[Frontiers in Bioscience 3, d194-207, February 15, 1998]

	[Frontiers in Bioscience 3, d194-207, February 15, 1998] Reprints PubMed CAVEAT LECTOR
	VASOPRESSIN SIGNALING PATHWAYS IN VASCULAR SMOOTH MUSCLE Raphael A. Nemenoff Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262 Received 1/21/98 Accepted 2/4/98 9. REFERENCES 1. Lolait, S. J., O'Carroll, A.-M., McBride, O. W., Konig, M., Morel, A. and Brownstein, M. J.: Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus. Nature, 357, 336-339 (1992) 2. Morel, A., O'Carroll, A.-M., Brownstein, M. J. and Lolait, S. J.: Molecular cloning and expression of a rat V1a arginine vasopressin receptor. Nature, 356, 523-526 (1992) 3. Sugimoto, T., Saito, M., Mochizuki, S., Watanabe, Y., Hashimoto, S. and Kawashima, H.: Molecular cloning and functional expression of a cDNA encoding the human V1b vasopressin receptor. J. Biol. Chem., 269, 27088-27092 (1994) 4. Yamamura, Y., Ogawa, H., Chihara, T., Kondo, K., Onogawa, T., Nakamura, S., Mori, T., Tominaga, M. and Yabuuchi, Y.: OPC-21268, An Orally Effective, Nonpeptide Vasopressin V1 Receptor Antagonist. Science, 252, 572-574 (1991) 5. Yamamura, Y., Ogawa, H., Yamashita, H., Chihara, T., Miyamoto, H., Nakamura, S., Onogawa, t., Yamashita, T., Hosokawa, T., Mori, T. and al.: Characterization of a novel aquaretic agent, OPC-32160, as an orally effective, nonpeptide vasopressin V2 receptor antagonist. Br. J. Pharmacol., 105, 787-791 (1992) 6. Serradeil-Le Gal, C., Herbert, J. M., Delisee, C., Schaeffer, P., Raufaste, D., Garcia, C., Dol, F., Marty, E., Maffrand, J. P. and Le Fur, G.: Effect of SR-49059, a vasopressin V1a antagonist, on human vascular smooth muscle cells. Am .J. Physiol., 268, H404-H410 (1995) 7. Serradeil-Le Gal, C., Lacour, C., Velette, G., Garcia, G., Foulon, L., Galindo, G., Bankir, L., Pouzet, B., Guillon, G., Barberis, C., Chicot, D., Jard, S., Vilain, P., Garcia, C., Marty, E., Raufaste, D., Brossard, G., Nisato, D., Maffrand, J. P. and G., L. F.: Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. J. Clin. Invest., 98, 2729-2738 (1996) 8. Caramelo, C., Tsai, P., Okada, K., Briner, V. A. and Schrier, R. W.: Mechanisms of rapid desensitization to arginine vasopressin in vascular smooth muscle cells. Am. J. Physiol., 260, F46-F52 (1991) 9. Briner, V. A., Williams, B., Tsai, P. and Schrier, R. W.: Demonstration of processing and recycling of biologically active V1 vasopressin receptors in vascular smooth muscle. Proc. Natl. Acad. Sci. USA, 89, 2854-2858 (1992) 10. Daaka, Y., Luttrell, L. M., Ahn, S., Della Rocca, G. J., Ferguson, S. S. G., Caron, M. G. and Lefkowitz, R. J.: Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. J. Biol. Chem., 273, 685-688 (1998) 11. Li, X., Kribben, A., Wieder, E. D., Tsai, P., Nemenoff, R. A. and Schrier, R. W.: Inhibition of vasopressin action in vascular smooth muscle by the V1-antagonist OPC-21268. Hypertension, 23, 217-222 (1993) 12. Frid, M. G., Moiseeva, E. P. and Stenmark, K. R.: Multiple phenotypically distinct smooth muscle cell populations exist in the adult and developing bovine pulmonary arterial media in vivo. Circ. Res., 75, 669-681 (1994) 13. Chamley-Campbell, J., Campbell, G. R. and Ross, R.: The smooth muscle cell in culture. Physiol. Rev., 59, 1-61 (1979) 14. Campbell, J. H., Tachas, G., Black, M. J., Cockerill, G. and Campbell, G. R.: Molecular biology of vascular hypertrophy. Basic. Res. Cardiol., 86, 3-11 (1991) 15. Owens, G. K.: Regulation of differentiation of vascular smooth muscle cells. Physiol. Rev., 75, 487-517 (1995) 16. Briner, V. A., Tsai, P., Choong, H. L. and Schrier, R. W.: Comparative effects of arginine vasopressin and oxytocin on contraction in cell culture systems. Am. J. Physiol., 263, F222-F227 (1992) 17. Meyer-Lehnert, H., P., T., Caramelo, C. and Schrier, R. W.: ANF inhibits vasopressin-induced Ca2+ mobilization and contraction in glomerular mesangial cells. Am. J. Physiol., 255, F771-F780 (1988) 18. Takeda, K., Meyer-Lehnert, H., Kim, J. K. and Schrier, R. W.: Effect of angiotensin II on Ca2+ kinetics and contraction in cultured rat glomerular mesangial cells. Am. J. Physiol., 254, F254-F266 (1988) 19Murray, T. R., Marshall, B. E. and Macarak, E. J.: C.ontraction of vascular smooth muscle in cell culture. J. Cell. Physiol., 143, 26-38 (1990) 20. Berk, B. C., Elder, E. and Mitsuka, M.: Hypertrophy and hyperplasia cause differing effects on vascular smooth muscle cell Na+/H+ exchange and intracellular pH. J. Biol. Chem., 265, 19632-19637 (1990) 21. Geisterfer, A. A. T. and Owens, G. K.: Arginine vasopressin-induced hypertrophy of cultured rat aortic smooth muscle cells. Hypertension, 14, 413-420 (1989) 22. Geisterfer, A. A. T., Peach, M. J. and Owens, G. K.: Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ. Res., 62, 749-756 (1988) 23. Gibbons, G. H., Pratt, R. E. and Dzau, V. J.: Vascular smooth muscle cell hypertrophy vs. hyperplasia: autocrine transforming growth factor b1 expression determines growth response to angiotensin II. J. Clin. Invest., 90, 456-461 (1992) 24. Turla, M. B., Thompson, M. M., Corjay, M. H. and Owens, G. K.: Mechanisms of angiotensin II- and arginine vasopressin-induced increases in protein synthesis and content in cultured rat aortic smooth muscle cells. Circulation Res., 68, 288-299 (1991) 25. Owens, G. K., Geisterfer, A. A. T., Yang, Y. W.-H. and Komoriya, A.: Transforming growth factor-b-induced growth inhibition and cellular hypertrophy in cultured vascular smooth muscle cells. J. Cell Biol., 107, 771-780 (1988) 26. Thibonnier, M., Bayer, A. L., Simonson, M. S. and Kester, M.: Multiple signaling pathways of V1-vascular AVP receptors of A7r5 cells. Endocrinology, 129, 2845-2856 (1991) 27. Li, X., Tsai, P., Wieder, E. D., Kribben, A., Van Putten, V., Schrier, R. W. and Nemenoff, R. A.: Vascular smooth muscle cells grown on Matrigel: a model of the contractile phenotype with decreased activation of MAP kinase. J. Biol. Chem., 269, 19653-19658 (1994) 28. Li, X., Van Putten, V., Zarinetchi, F., Nicks, M. E., Thaler, S., Heasley, L. E. and Nemenoff, R. A.: Suppression of smooth muscle a-actin by platelet-derived growth factor in vascular smooth muscle cells involves Ras and cytosolic PLA2. Biochem. J., 327, 709-716 (1997) 29. Higashita, R., Li, L., Van Putten, V., Yamamura, M., Zarinetchi, F., Heasley, L. E. and Nemenoff, R. A.: Ga16 mimics vasoconstrictor action to induce smooth muscle a-actin in vascular smooth muscle cells through a Jun-amino terminal kinase dependent pathway. J. Biol. Chem., 272, 25845-25850 (1997) 30. Thibonnier, M.: Signal transduction of V1-vascular vasopressin receptors. Regulatory Peptides, 38, 1-11 (1992) 31. Johnson, E. M., Theler, J.-M., Capponi, A. M. and Vallotton, M. B.: Characterization of oscillations in cytosolic free Ca2+ concentration and measurement of cytosolic Na+ concentration changes evoked by angiotensin II and vasopressin in individual rat aortic smooth muscle cells. J. Biol. Chem., 266, 12618-12626 (1991) 32. Capponi, A. M., Lew, P. D. and Vallotton, M. B.: Cytosolic free calcium levels in monolayers of cultured rat aortic smooth muscle cells. J. Biol. Chem., 260, 7836-7842 (1985) 33. Caramelo, C., Okada, K., Tsai, P., Linas, S. L. and Schrier, R. W.: Interaction of arginine vasopressin and angiotensin II on Ca2+ in vascular smooth muscle cells. Kidney Int., 38, 47-54 (1990) 34. Nakajima, T., Hazama, H., Hamada, E., Wu, S. N., Igarishi, K., Yamashita, T., Seyama, Y., Omata, M. and Kurachi, Y.: Endothelin-1 and vasopressin activate Ca(2+)-permeable non-selective cation channels in aortic smooth muscle cells: mechanism of receptor-mediated Ca2+ influx. J. Mol. Cell. Cardiol., 28, 707-722 (1996) 35. Ruegg, U. T., Wallnofer, A., Weir, S. and Cauvin, C.: Receptor operated calcium-permeable channels in vascular smooth muscle. J. Cardiovasc. Pharmacol., 14, S49-S58 (1989) 36. Byron, K. and Taylor, C. W.: Vasopressin stimulation of Ca2+ mobilization, two bivalent cation entry pathways and Ca2+ efflux in A7r5 rat smooth muscle cells. J. Physiol. (Lond), 485, 455-468 (1995) 37. Stull, J. T., Gallagher, P. J., Herring, B. P. and Kamm, K. E.: Vascular smooth muscle contractile elements: cellular regulation. Hypertension, 17, 723-732 (1991) 38. Hathaway, D. R., March, K. L., Lash, J. A., Adam, L. P. and Wilensky, R. L.: Vascular smooth muscle: a review of the molecular basis of contractility. Circulation, 83, 382-390 (1991) 39. Kureishi, Y., Kobayashi, S., Amano, M., Kimura, K., Kanaide, H., Nakano, T., Kaibuchi, K. and Ito, M.: Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation. J. Biol. Chem., 272, 12257-12260 (1997) 40. Zhang, J., Sato, M., Duzic, E., Kubalak, S. W., Lanier, S. M. and Webb, J. G.: Adenylyl cyclase isoforms and vasopressin enhancement of agonist-stimulated cAMP in vascular smooth muscle cells. Am. J. Physiol., 273, H971-H980 (1997) 41. Ohara, O., Nakano, T., Teraoka, H. and Arita, H.: cAMP negatively regulates mRNA levels of actin and tropomyosin in rat cultured vascular smooth muscle. J. Biochem., 109, 834-839 (1991) 42. Abraham, S. T., Benscoter, H. A., Schworer, C. M. and Singer, H. A.: A role for Ca2+/calmodulin-dependent protein kinase II in the mitogen-activated protein kinase signaling cascade of cultured rat aortic vascular smooth muscle cells. Circ. Res., 81, 575-584 (1997) 43. Gronich, J. H., Bonventre, J. V. and Nemenoff, R. A.: Identification and characterization of a hormonally regulated form of phospholipase A2 in rat renal mesangial cells. J. Biol. Chem., 263, 16645-16651 (1988) 44. Herskowitz, I.: MAP kinase pathways in yeast: for mating and more. Cell, 80, 187-197 (1995) 45. Blumer, K. J. and Johnson, G. L.: Diversity in function and regulation of MAP kinase pathways. Trends Biochem. Sci., 19, 236-240 (1994) 46. Cano, E. and Mahadevan, L. C.: Parallel signal processing among mammalian MAPKs. Trends Biochem. Sci., 20, 117-122 (1995) 47. Davis, R. J.: The mitogen-activated protein kinase signal transduction pathway. J. Biol. Chem., 268, 14553-14556 (1993) 48. Karin, M.: Signal transduction from cell surface to nucleus in development and disease. FASEB J., 6, 2581-2590 (1992) 49. Macara, I. G., Lounsbury, K. M., Richards, S. A., McKiernan, C. and Bar-Sagi, D.: The Ras superfamily of GTPases. FASEB J., 10, 625-630 (1996) 50. Marshall, M.: Ras target proteins in eukaryotic cells. FASEB J., 9, 1311-1318 (1995) 51. Pawson, T. and Scott, J. D.: Signaling through scaffold, anchoring, and adaptor proteins. Science, 278, 2075-2080 (1997) 52. Treisman, R.: Regulation of transcription by MAP kinase cascades. Curr. Opinion Cell Biol., 8, 205-215 (1996) 53. Schlessinger, J.: How receptor tyrosine kinases activate Ras. TIBS, 18, 273-275 (1993) 54. Kyriakis, J. M., App, H., Zhang, X.-F., Banerjee, P., Brautigan, D. L., Rapp, U. R. and Avruch, J.: Raf-1 activates MAP kinase-kinase. Nature, 358, 417-421 (1992) 55. Howe, L. R., Leevers, S. J., Gomez, N., Nakielny, S., Cohen, P. and Marshall, C. J.: Activation of the MAP kinase pathway by the protein kinase raf. Cell, 71, 335-342 (1992) 56. Satoh, T., Endo, M., Nakafuku, M., Nakamura, S. and Kaziro, Y.: Platelet-derived growth factor stimulates formation of active p21ras GTP complex in swiss mouse 3T3 cells. Proc. Natl. Acad. Sci. USA., 87, 5993-5997 (1990) 57. Minden, A., Lin, A., McMahon, M., Lange-Carter, C., Derijard, B., Davis, R. J., Johnson, G. L. and Karin, M.: Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science, 266, 1719-1723 (1994) 58. Dent, P., Haser, W., Haystead, T. A., Vicent, L. A., Roberts, T. M. and Sturgill, T. W.: Activation of mitogen-activated protein kinase kinase by v-Raf in 3T3 cells and in vitro. Science, 257, 1404-1407 (1992) 59. Kribben, A., Li, X., Wieder, E. D., Van Putten, V., Schrier, R. W. and Nemenoff, R. A.: AVP-induced activation of MAP kinase in vascular smooth muscle cells is mediated through protein kinase C. Am. J. Physiol., 265, C939-C945 (1993) 60. Takahashi, T., Kawahara, Y., Okuda, M., Ueno, H., Takeshita, A. and Yokoyama, M.: Angiotensin II stimulates mitogen-activated protein kinases and protein synthesis by a Ras-independent pathway in vascular smooth muscle cells. J. Biol. Chem., 272, 16018-16022 (1997) 61. Cowley, S., Paterson, H., Kemp, P. and Marshall, C. J.: Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell, 77, 841-852 (1994) 62. Gille, H., Sharrocks, A. D. and Shaw, P. E.: Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature, 358, 414-417 (1992) 63. Nemenoff, R. A., Winitz, S., Qian, N.-X., Van Putten, V., Johnson, G. L. and Heasley, L. E.: Phosphorylation and activation of a high molecular weight form of phospholipase A2 by p42 MAP kinase and protein kinase C. J. Biol. Chem., 268, 1960-1964 (1993) 64. Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J. and Saltiel, A. R.: A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl. Acad. Sci. USA, 92, 7686-7689 (1995) 65. Coso, O. A., Chiariello, M., Kalinec, G., Kyriakis, J. M., Woodgett, J. and Gutkind, J. S.: Transforming G protein-coupled receptors potently activate JNK(SAPK). J. Biol. Chem., 270, 5620-5624 (1995) 66. Sanchez, I., Hughes, R. T., Mayer, B. J., Yee, K., Woodgett, J. R., Avruch, J., Kyriakis, J. M. and Zon, L. I.: Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature, 372, 794-798 (1994) 67. Shapiro, P. S., Evans, J. N., Davis, R. J. and Posada, J. A.: The seven-transmembrane-spanning receptors for endothelin and thrombin cause proliferation of airway smooth muscle cells and activation of the extracellular regulated kinase and c-Jun NH2-terminal kinase groups of mitogen-activated protein kinases. J. Biol. Chem., 271, 5750-5754 (1996) 68. Minden, A., Lin, A., Claret, F.-X., Abo, A. and Karin, M.: Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell, 81, 1147-1157 (1995) 69. Kyriakis, J. M., Banerjee, P., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J. and Woodgett, J. R.: The stress-activated protein kinase subfamily of c-Jun kinases. Nature, 369, 156-160 (1994) 70. Coso, O. A., Montaner, S., Fromm, C., Lacal, J. C., Prywes, R., Teramoto, H. and Gutkind, J. S.: Signaling from G-protein-coupled receptros to the c-jun promoter involves the MEF2 transcription factor. Evidence for a novel c-jun aminot terminal kinase-independent pathway. J. Biol. Chem., 272, 20691-20697 (1997) 71. Derijard, B., Hibi, M., Wu, I.-H., Barrett, T., Su, B., Deng, T., Karin, M. and Davis, R. J.: JNK1: a protein kinase stimulated by UV light and Ha-ras that binds and phosphorylates the c-Jun activation domain. Cell, 76, 1025-1037 (1994) 72. Kallunki, T., Su, B., Tsigelny, I., Sluss, H. K., Derijard, B., Moore, G., Davis, R. and Karin, M.: JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes Dev., 8, 2996-3007 (1994) 73. Sluss, H. K., Barrett, T., Derijard, B. and Davis, R. J.: Signal transduction by tumor necrosis factor mediated by JNK protein kinases. Mol. Cell. Biol., 14, 8376-8384 (1994) 74. Gupta, S., Barrett, T., Whitmarsh, A. J., Derijard, B. and Davis, R. J.: Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J., 15, 2760-2770 (1996) 75. Whitmarsh, A. J., Shore, P., Sharrocks, A. D. and Davis, R. J.: Integration of MAP kinase signal transduction pathways at the serum response element. Science, 269, 403-407 (1995) 76. Tournier, C., Whitmarsh, A. J., Canavagh, J., Barrett, T. and Davis, R. J.: Miotgen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase. Proc. Natl. Acad. Sci. USA, 94, 7337-7342 (1997) 77. Ruis, H. and Schuller, C.: Stress signaling in yeast. Bioessays, 17, 959-965 (1995) 78. Kramer, R. M., Roberts, E. F., Strifler, B. A. and Johnstone, E. M.: Thrombin induces activation of p38 MAP kinase in human platelets. J. Biol. Chem., 270, 27395-27398 (1995) 79. Lee, J. C., Laydon, J. T., McDonnell, P. C., Gallagher, T. F., Kumar, S., Green, D., McNulty, D., Blumenthal, M. J., Heys, J. R., Landvatter, S. W., Strickler, J. E., McLuaghlin, M. M., Siemens, I. R., Fisher, S. M., Livi, G. P., White, J. R., Adams, J. L. and Young, P. R.: A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature, 372, 739-746 (1994) 80. Schror, K. and Weber, A.-A.: Roles of vasodilatory prostaglandins in mitogenesis of vascular smooth muscle cells. Agents Actions Suppl., 48, 63-91 (1997) 81. Larrue, J., Dorian, B., Daret, D., Demond-Henri, J. and Bricaud, H.: Role of cyclic AMP in the regulation of prostacyclin synthesis by cultured vascular smooth muscle cells. Adv. Cyclic Nucl. Prot. Phosph. Res., 17, 585-592 (1984) 82. Gronich, J. H., Bonventre, J. V. and Nemenoff, R. A.: Purification of Phospholipase A2 from Rat Kidney. Biochem. J., 271, 37-43 (1990) 83. Sharp, J. D., White, D. L., Chiou, X. G., Goodson, T., Gamboa, G. C., McClure, D., Burgett, S., Hoskins, J., Skatrud, P. L., Sportsman, J. R., Becker, G. W., Kang, L. H., Roberts, E. F. and Kramer, R. M.: Molecular cloning and expression of human Ca2+-sensitive cytosolic phospholipase A2. J. Biol. Chem., 266, 14850-14853 (1991) 84. Clark, M. A., Conway, T. M., Shorr, R. G. L. and Crooke, S. T.: Identification and isolation of a mammalian protein which is antigenically and functionally related to the phospholipase A2 stimulatory peptide melittin. J. Biol. Chem., 262, 4402-4406 (1987) 85. Clark, J. D., Milona, N. and Knopf, J. L.: Purification of a 110-kilodalton cytosolic phospholipase A2 from the human monocytic cell line U937. Proc. Natl. Acad. Sci. USA, 87, 7708-7712 (1990) 86. Channon, J. Y. and Leslie, C. C.: A calcium-dependent mechanism for associating a soluble arachidonyl-hydrolyzing phospholipase A2 with membrane in the macrophage cell line RAW 264.7. J. Biol. Chem., 265, 5409-5413 (1990) 87. Glover, S., Bayburt, T., Jonas, M., Chi, E. and Gelb, M. H.: Translocation of the 85-kDa phospholipase A2 from cytosol to the nuclear envelope in rat basophilic leukemia cells stimulated with calcium ionophore or IgE/antigen. J. Biol. Chem., 270, 15359-15367 (1995) 88. Lin, L.-L., Wartmann, M., Lin, A. Y., Knopf, J. L., Seth, A. and Davis, R. J.: cPLA2 is phosphorylated and activated by MAP kinase. Cell, 72, 269-278 (1993) 89. Hazen, S. L., Stuppy, R. J. and Gross, R. W.: Purification and characterization of canine myocardial cytosolic phospholipase A2. J. Biol. Chem., 265, 10622-10630 (1990) 90. Lehman, J. J., Brown, K. A., Ramanadham, S., Turk, J. and Gross, R. W.: Arachidonic acid release from aortic smooth muscle cells induced by [Arg8]vasopressin is largely mediated by calcium-independent phospholipase A2. J. Biol. Chem., 268, 20713-20716 (1993) 91. Wolf, M. J., Wang, J., Turk, J. and Gross, R. W.: Depletion of intracellular calcium stores activates smooth muscle cell calcium-independent phospholipase A2. A novel mechanism underlyign arachidonic acid mobilization. J. Biol. Chem., 272, 1522-1526 (1997) 92. Kujubu, D. A., Fletcher, B. S., Varnum, B. C., Lim, R. W. and Herschman, H. R.: TIS10, a phorbol ester tumor promoter inducible mRNA from Swiss 3T3 cells encodes a novel prostaglandin synthase/cyclooxygenase homologue. J. Biol. Chem., 266, 12866-12872 (1991) 93. Xie, W. and Herschman, H. R.: Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet-derived growth factor and serum. J. Biol. Chem., 271, 31742-31748 (1996) 94. Sasaguri, T., Masuda, J., Shimokado, K., Yokota, T., Kosaka, C., Fujishima, M. and Ogata, J.: Prostaglandins A and J arrest the cell cycle of cultured vascular smooth muscle cells without suppression of c-myc expression. Exp. Cell Res., 200, 351-357 (1992) 95. Anderson, K. M., Roshak, A., Winkler, J. D., McCord, M. and Marshall, L. A.: Cytosolic 85-kDa phospholipase A2-mediated release of arachidonic acid is critical for proliferation of vascular smooth muscle cells. J. Biol. Chem., 272, 30504-30511 (1997) 96. Rao, G. N., Baas, A. S., Glasgow, W. C., Eling, T. E., Runge, M. S. and Alexander, R. W.: Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells. J. Biol. Chem., 269, 32586-32591 (1994) 97. Welsh, C. J., Schmeichel, K., Cao, H. and Chabbott, H.: Vasopressin stimulates phospholipase D activity against phosphatidylcholine in vascular smooth muscle cells. Lipids, 25, 675-684 (1990) 98. Exton, J. H.: Signaling through Phosphatidylcholine Breakdown. J. Biol. Chem., 265, 1-4 (1990) 99. Billah, M. M., Eckel, S., Mullmann, T. J., Egan, R. W. and Siegel, M. I.: Phosphatidylcholine Hydrolysis by Phospholipase D Determines Phosphatidate and Diglyceride Levels in Chemotactic Peptide-stimulated Human Neutrophils. J. Biol. Chem., 264, 17069-17077 (1989) 100. Moolenar, W. H., Kruijer, W., Tilly, B. C., Verlaan, I., Bierman, A. J. and de Laat, S. W.: Growth factor-like action of phosphatidic acid. Nature, 323, 171-173 (1986) 101.van Corven, E. J., Groenink, A., Jalink, K., Eichholtz, T. and Moolenaar, W. H.: Lysophosphatidate-Induced Cell Proliferation: Identification and Dissection of Signaling Pathways Mediated by G proteins. Cell, 59, 45-54 (1989) 102. Sellmayer, A., Uedelhoven, W. M., Weber, P. C. and Bonventre, J. V.: Endogenous Non-cyclooxygenase Metabolites of Arachidonic Acid Modulate Growth and mRNA Levels of Early Response Genes in Rat Mesangial Cells. J. Biol. Chem., 266, 3800-3807 (1991) 103.Thibonnier, M., Bayer, A. L., Simonson, M. S. and Koop, D. R.: V1-vascular AVP receptors of A7r5 cells activate the arachidonic acid cyclooxygenase and epoxygenase pathways. J. Am. Soc. Nephrol., 2, 432 (1991) 104. Hill, C. S. and Treisman, R.: Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell, 80, 199-211 (1994) 105. Treisman, R.: Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J., 6, 2711-2717 (1987) 106. Hill, C. S. and Treisman, R.: Differential regulation of c-fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors. EMBO J., 14, 5037-5047 (1996) 107. Naftilan, A. J., Pratt, R. E. and Dzau, V. J.: Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. J. Clin. Invest., 83, 1419-1424 (1989) 108. Blank, R. S., McQuinn, T. C., Yin, K. C., Thompson, M. M., Takeyasu, K., Schwartz, R. J. and Owens, G. K.: Elements of the smooth muscle a-actin promoter required in cis for transcriptional activation in smooth muscle. J. Biol. Chem., 267, 984-989 (1992) 109. Van Putten, V., Li, X., Maselli, J. and Nemenoff, R. A.: Regulation of smooth muscle-a-actin promoter by vasopressin and PDGF in rat aortic vascular smooth muscle cells. Circ. Res., 75, 1126-1130 (1994) 110. Hautmann, M. B., Thompson, M. M., Swartz, E. A., Olson, E. N. and Owens, G. K.: Angiotensin II-induced stimulation of smooth muscle a-actin expression by serum response factor and the homeodomain transcription factor MHox. Circ. Res., 81, 600-610 (1997) 111. Hautmann, M. B., Madsen, C. S. and Owens, G. K.: A transforming growth factor b (TGFb) control element drives TGFb-induced stimulation of smooth muscle a-actin gene expression in concert with two CArG elements. J. Biol. Chem., 272, 10948-10956 (1997) 112. Muscat, G. E. O., Gustafson, T. A. and Kedes, L.: A common factor regulates skeletal and cardiac a-actin gene transcription in muscle. Mol. Cell. Biol., 8, 4120-4133 (1988) 113. MacLellan, W. r., Lee, T.-C., Schwartz, R. J. and Schneider, M. D.: Transforming growth factor-b response elements of the skeletal a-actin gene. J. Biol. Chem., 269, 16754-16760 (1994) 114. Catala, F., Wanner, R., Barton, P., Cohen, A., Wright, W. and Buckingham, M.: A skeletal muscle-specific enhancer regulated by factors binding to E and CArG boxes is present in the promoter of the mouse mysoin light chain 1A gene. Mol. Cell. Biol., 15, 4585-4596 (1995) 115. Bushel, P., Kim, J. H., Chang, W., Catino, J. J., Ruley, H. E. and Kumar, C. C.: Two serum response elements mediate transcriptional repression of human smooth muscle a-actin promoter in ras-transformed cells. Oncogene, 10, 1361-1370 (1995) 116. Lee, T.-C., Chow, K.-L., Fang, P. and Schwartz, R. J.: Activation of skeletal a-actin gene transcription: the cooperative formation of serum response factor-binding complexes ofver positive cis-acting promoter serum response elements displaces a negative factor enriched in replicating myoblasts and nonmyogenic cells. Mol. Cell. Biol., 11, 5090-5100 (1991) 117. Boxer, L. M., Miwa, T., Gustafson, T. A. and Kedes, L.: Identification and characterization of a factor that binds to two human sarcomeric actin promoters. J. Biol. Chem., 264, 1284-1292 (1989) 118. Shimuzu, R. T., Blank, R. S., Jervis, R., Lawrenz-Smith, S. C. and Owens, G. K.: The smooth muscle a-actin gene promoter is differentially regulated in smooth muscle cells versus non-smooth muscle cells. J. Biol. Chem., 270, 7631-7643 (1995) 119. Paradis, P., MacLellan, W. R., Belaguli, N. S., Schwartz, R. J. and Schneider, M. D.: Serum response factor mediates AP-1-dependent induction of the skeletal a-actin promoter in ventricular myocytes. J. Biol. Chem., 271, 10827-10833 (1996) 120. Groisman, R., Masutani, H., Leibovitch, M.-P., Robin, P., Soudant, I., Trouche, D. and Harel-Bellan, A.: Physical interaction between the mitogen-responsive serum-response factor and myogenic basic-helix-loop-helix proteins. J. Biol. Chem., 271, 5258-5264 (1996) 121. Caramelo, C., Okada, K., Tsai, P. and Schrier, R. W.: Phorbol Esters and arginine vasopressin in vascular smooth muscle cell activation. Am. J. Physiol., 256, F875-F881 (1989) 122. Ganz, M. B., Boyarsky, G., Boron, W. and Sterzel, R. B.: Effects of angiotensin II and vasopressin on intracellular pH of glomerular mesangial cells. Am. J. Physiol., 254, F787-F794 (1988) 123. Mayer, B. and Hemmens, B.: Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem. Sci., 22, 477-481 (1997) 124. Kusano, E., Tian, S., Umino, T., Tetsuka, T., Ando, Y. and Asano, Y.: Arginine vasopressin inhibits interleukin-1 beta-stimulated nitric oxide and cyclic guanosine monophosphate produciton via the V1 receptor in cultured rat vascular smooth muscle cells. J. Hypertens., 15, 627-632 (1997) 125. Yamamoto, K., Ikeda, U., Okada, K., Saito, T. and Shimada, K.: Arginine vasopressin inhibits nitric oxide synthesis in cytokine-stimulated vascular smooth muscle cells. Hypertens. Res., 20, 209-216 (1997) 126. Hamet, P., Hadrava, V., Kruppa, U. and Tremblay, J.: Vascular smooth muscle cell hyperresponsiveness to growth factors in hypertension. J. Hypertens., 6, S36-S39 (1988) 127. Paquet, J. L., Baudoin-Legros, M., Brunelle, G. and Meyer, P.: Angiotensin II-induced proliferation of aortic myocytes in SHR. J. Hypertens., 8, 565-572 (1990) 128. Bendhack, L. M., Sharma, R. V. and Bhalla, R. C.: Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats. Hypertension, 19, II-142-II-148 (1992) 129. Paquet, J.-L., Baudouin-Legros, M., Brunelle, G. and Meyer, P.: Hyperactivation of phospholipase C does not support the enhanced proliferation of aortic smooth muscle cells from spontaneously hypertensive rats. Am. J. Hypertens., 4, 651-660 (1991) 130. Symons, M.: Rho family GTPases: the cytoskeleton and beyond. Trends Biochem. Sci., 21, 178-181 (1996) 131Ridley, A. J. and Hall, A.: The small GTP-binding protein rho regulates the assemblyof focal adhesions and actin stress fibers in response to growth factors. Cell, 70, 389-399 (1992) 132. Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., Iwamatsu, A. and Kaibuchi, K.: Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science, 273, 245-248 (1996) 133. Frid, M. G., Aldashev, A. A., Dempsey, E. C. and Stenmark, K. R.: Smooth muiscle cells isolated from discrete compartments of the mature vascular media exhibit unique phenotypes and distinct growth capabilities. Circ. Res., 81, 940-952 (1997) Text footnotes: 1. The abbreviations used are: VSMC, vascular smooth muscle cells; MEM, minimal essential media; SM-alpha-actin, smooth muscle- alpha-actin; PCR, polymerase chain reaction; CAT, chloramphenicol acetyl transferase; FCS, fetal calf serum; PAGE, polyacrylaminde gel electrophoresis; PDGF, platelet derived growth factor; PMA, phorbol 12-myristate 13-acetate; AVP, arginine vasopressin; AII, angiotensin II; JNK, cJun NH2-terminal kinase. 2. R.A. Nemenoff, unpublished observations

[Frontiers in Bioscience 3, d194-207, February 15, 1998]
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CAVEAT LECTOR

VASOPRESSIN SIGNALING PATHWAYS IN VASCULAR SMOOTH MUSCLE

Raphael A. Nemenoff

Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262

Received 1/21/98 Accepted 2/4/98

9. REFERENCES

1. Lolait, S. J., O'Carroll, A.-M., McBride, O. W., Konig, M., Morel, A. and Brownstein, M. J.: Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus. Nature, 357, 336-339 (1992)

2. Morel, A., O'Carroll, A.-M., Brownstein, M. J. and Lolait, S. J.: Molecular cloning and expression of a rat V1a arginine vasopressin receptor. Nature, 356, 523-526 (1992)

3. Sugimoto, T., Saito, M., Mochizuki, S., Watanabe, Y., Hashimoto, S. and Kawashima, H.: Molecular cloning and functional expression of a cDNA encoding the human V1b vasopressin receptor. J. Biol. Chem., 269, 27088-27092 (1994)

4. Yamamura, Y., Ogawa, H., Chihara, T., Kondo, K., Onogawa, T., Nakamura, S., Mori, T., Tominaga, M. and Yabuuchi, Y.: OPC-21268, An Orally Effective, Nonpeptide Vasopressin V1 Receptor Antagonist. Science, 252, 572-574 (1991)

5. Yamamura, Y., Ogawa, H., Yamashita, H., Chihara, T., Miyamoto, H., Nakamura, S., Onogawa, t., Yamashita, T., Hosokawa, T., Mori, T. and al.: Characterization of a novel aquaretic agent, OPC-32160, as an orally effective, nonpeptide vasopressin V2 receptor antagonist. Br. J. Pharmacol., 105, 787-791 (1992)

6. Serradeil-Le Gal, C., Herbert, J. M., Delisee, C., Schaeffer, P., Raufaste, D., Garcia, C., Dol, F., Marty, E., Maffrand, J. P. and Le Fur, G.: Effect of SR-49059, a vasopressin V1a antagonist, on human vascular smooth muscle cells. Am .J. Physiol., 268, H404-H410 (1995)

7. Serradeil-Le Gal, C., Lacour, C., Velette, G., Garcia, G., Foulon, L., Galindo, G., Bankir, L., Pouzet, B., Guillon, G., Barberis, C., Chicot, D., Jard, S., Vilain, P., Garcia, C., Marty, E., Raufaste, D., Brossard, G., Nisato, D., Maffrand, J. P. and G., L. F.: Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. J. Clin. Invest., 98, 2729-2738 (1996)

8. Caramelo, C., Tsai, P., Okada, K., Briner, V. A. and Schrier, R. W.: Mechanisms of rapid desensitization to arginine vasopressin in vascular smooth muscle cells. Am. J. Physiol., 260, F46-F52 (1991)

9. Briner, V. A., Williams, B., Tsai, P. and Schrier, R. W.: Demonstration of processing and recycling of biologically active V1 vasopressin receptors in vascular smooth muscle. Proc. Natl. Acad. Sci. USA, 89, 2854-2858 (1992)

10. Daaka, Y., Luttrell, L. M., Ahn, S., Della Rocca, G. J., Ferguson, S. S. G., Caron, M. G. and Lefkowitz, R. J.: Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. J. Biol. Chem., 273, 685-688 (1998)

11. Li, X., Kribben, A., Wieder, E. D., Tsai, P., Nemenoff, R. A. and Schrier, R. W.: Inhibition of vasopressin action in vascular smooth muscle by the V1-antagonist OPC-21268. Hypertension, 23, 217-222 (1993)

12. Frid, M. G., Moiseeva, E. P. and Stenmark, K. R.: Multiple phenotypically distinct smooth muscle cell populations exist in the adult and developing bovine pulmonary arterial media in vivo. Circ. Res., 75, 669-681 (1994)

13. Chamley-Campbell, J., Campbell, G. R. and Ross, R.: The smooth muscle cell in culture. Physiol. Rev., 59, 1-61 (1979)

14. Campbell, J. H., Tachas, G., Black, M. J., Cockerill, G. and Campbell, G. R.: Molecular biology of vascular hypertrophy. Basic. Res. Cardiol., 86, 3-11 (1991)

15. Owens, G. K.: Regulation of differentiation of vascular smooth muscle cells. Physiol. Rev., 75, 487-517 (1995)

16. Briner, V. A., Tsai, P., Choong, H. L. and Schrier, R. W.: Comparative effects of arginine vasopressin and oxytocin on contraction in cell culture systems. Am. J. Physiol., 263, F222-F227 (1992)

17. Meyer-Lehnert, H., P., T., Caramelo, C. and Schrier, R. W.: ANF inhibits vasopressin-induced Ca2+ mobilization and contraction in glomerular mesangial cells. Am. J. Physiol., 255, F771-F780 (1988)

18. Takeda, K., Meyer-Lehnert, H., Kim, J. K. and Schrier, R. W.: Effect of angiotensin II on Ca2+ kinetics and contraction in cultured rat glomerular mesangial cells. Am. J. Physiol., 254, F254-F266 (1988)

19Murray, T. R., Marshall, B. E. and Macarak, E. J.: C.ontraction of vascular smooth muscle in cell culture. J. Cell. Physiol., 143, 26-38 (1990)

20. Berk, B. C., Elder, E. and Mitsuka, M.: Hypertrophy and hyperplasia cause differing effects on vascular smooth muscle cell Na+/H+ exchange and intracellular pH. J. Biol. Chem., 265, 19632-19637 (1990)

21. Geisterfer, A. A. T. and Owens, G. K.: Arginine vasopressin-induced hypertrophy of cultured rat aortic smooth muscle cells. Hypertension, 14, 413-420 (1989)

22. Geisterfer, A. A. T., Peach, M. J. and Owens, G. K.: Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ. Res., 62, 749-756 (1988)

23. Gibbons, G. H., Pratt, R. E. and Dzau, V. J.: Vascular smooth muscle cell hypertrophy vs. hyperplasia: autocrine transforming growth factor b1 expression determines growth response to angiotensin II. J. Clin. Invest., 90, 456-461 (1992)

24. Turla, M. B., Thompson, M. M., Corjay, M. H. and Owens, G. K.: Mechanisms of angiotensin II- and arginine vasopressin-induced increases in protein synthesis and content in cultured rat aortic smooth muscle cells. Circulation Res., 68, 288-299 (1991)

25. Owens, G. K., Geisterfer, A. A. T., Yang, Y. W.-H. and Komoriya, A.: Transforming growth factor-b-induced growth inhibition and cellular hypertrophy in cultured vascular smooth muscle cells. J. Cell Biol., 107, 771-780 (1988)

26. Thibonnier, M., Bayer, A. L., Simonson, M. S. and Kester, M.: Multiple signaling pathways of V1-vascular AVP receptors of A7r5 cells. Endocrinology, 129, 2845-2856 (1991)

27. Li, X., Tsai, P., Wieder, E. D., Kribben, A., Van Putten, V., Schrier, R. W. and Nemenoff, R. A.: Vascular smooth muscle cells grown on Matrigel: a model of the contractile phenotype with decreased activation of MAP kinase. J. Biol. Chem., 269, 19653-19658 (1994)

28. Li, X., Van Putten, V., Zarinetchi, F., Nicks, M. E., Thaler, S., Heasley, L. E. and Nemenoff, R. A.: Suppression of smooth muscle a-actin by platelet-derived growth factor in vascular smooth muscle cells involves Ras and cytosolic PLA2. Biochem. J., 327, 709-716 (1997)

29. Higashita, R., Li, L., Van Putten, V., Yamamura, M., Zarinetchi, F., Heasley, L. E. and Nemenoff, R. A.: Ga16 mimics vasoconstrictor action to induce smooth muscle a-actin in vascular smooth muscle cells through a Jun-amino terminal kinase dependent pathway. J. Biol. Chem., 272, 25845-25850 (1997)

30. Thibonnier, M.: Signal transduction of V1-vascular vasopressin receptors. Regulatory Peptides, 38, 1-11 (1992)

31. Johnson, E. M., Theler, J.-M., Capponi, A. M. and Vallotton, M. B.: Characterization of oscillations in cytosolic free Ca2+ concentration and measurement of cytosolic Na+ concentration changes evoked by angiotensin II and vasopressin in individual rat aortic smooth muscle cells. J. Biol. Chem., 266, 12618-12626 (1991)

32. Capponi, A. M., Lew, P. D. and Vallotton, M. B.: Cytosolic free calcium levels in monolayers of cultured rat aortic smooth muscle cells. J. Biol. Chem., 260, 7836-7842 (1985)

33. Caramelo, C., Okada, K., Tsai, P., Linas, S. L. and Schrier, R. W.: Interaction of arginine vasopressin and angiotensin II on Ca2+ in vascular smooth muscle cells. Kidney Int., 38, 47-54 (1990)

34. Nakajima, T., Hazama, H., Hamada, E., Wu, S. N., Igarishi, K., Yamashita, T., Seyama, Y., Omata, M. and Kurachi, Y.: Endothelin-1 and vasopressin activate Ca(2+)-permeable non-selective cation channels in aortic smooth muscle cells: mechanism of receptor-mediated Ca2+ influx. J. Mol. Cell. Cardiol., 28, 707-722 (1996)

35. Ruegg, U. T., Wallnofer, A., Weir, S. and Cauvin, C.: Receptor operated calcium-permeable channels in vascular smooth muscle. J. Cardiovasc. Pharmacol., 14, S49-S58 (1989)

36. Byron, K. and Taylor, C. W.: Vasopressin stimulation of Ca2+ mobilization, two bivalent cation entry pathways and Ca2+ efflux in A7r5 rat smooth muscle cells. J. Physiol. (Lond), 485, 455-468 (1995)

37. Stull, J. T., Gallagher, P. J., Herring, B. P. and Kamm, K. E.: Vascular smooth muscle contractile elements: cellular regulation. Hypertension, 17, 723-732 (1991)

38. Hathaway, D. R., March, K. L., Lash, J. A., Adam, L. P. and Wilensky, R. L.: Vascular smooth muscle: a review of the molecular basis of contractility. Circulation, 83, 382-390 (1991)

39. Kureishi, Y., Kobayashi, S., Amano, M., Kimura, K., Kanaide, H., Nakano, T., Kaibuchi, K. and Ito, M.: Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation. J. Biol. Chem., 272, 12257-12260 (1997)

40. Zhang, J., Sato, M., Duzic, E., Kubalak, S. W., Lanier, S. M. and Webb, J. G.: Adenylyl cyclase isoforms and vasopressin enhancement of agonist-stimulated cAMP in vascular smooth muscle cells. Am. J. Physiol., 273, H971-H980 (1997)

41. Ohara, O., Nakano, T., Teraoka, H. and Arita, H.: cAMP negatively regulates mRNA levels of actin and tropomyosin in rat cultured vascular smooth muscle. J. Biochem., 109, 834-839 (1991)

42. Abraham, S. T., Benscoter, H. A., Schworer, C. M. and Singer, H. A.: A role for Ca2+/calmodulin-dependent protein kinase II in the mitogen-activated protein kinase signaling cascade of cultured rat aortic vascular smooth muscle cells. Circ. Res., 81, 575-584 (1997)

43. Gronich, J. H., Bonventre, J. V. and Nemenoff, R. A.: Identification and characterization of a hormonally regulated form of phospholipase A2 in rat renal mesangial cells. J. Biol. Chem., 263, 16645-16651 (1988)

44. Herskowitz, I.: MAP kinase pathways in yeast: for mating and more. Cell, 80, 187-197 (1995)

45. Blumer, K. J. and Johnson, G. L.: Diversity in function and regulation of MAP kinase pathways. Trends Biochem. Sci., 19, 236-240 (1994)

46. Cano, E. and Mahadevan, L. C.: Parallel signal processing among mammalian MAPKs. Trends Biochem. Sci., 20, 117-122 (1995)

47. Davis, R. J.: The mitogen-activated protein kinase signal transduction pathway. J. Biol. Chem., 268, 14553-14556 (1993)

48. Karin, M.: Signal transduction from cell surface to nucleus in development and disease. FASEB J., 6, 2581-2590 (1992)

49. Macara, I. G., Lounsbury, K. M., Richards, S. A., McKiernan, C. and Bar-Sagi, D.: The Ras superfamily of GTPases. FASEB J., 10, 625-630 (1996)

50. Marshall, M.: Ras target proteins in eukaryotic cells. FASEB J., 9, 1311-1318 (1995)

51. Pawson, T. and Scott, J. D.: Signaling through scaffold, anchoring, and adaptor proteins. Science, 278, 2075-2080 (1997)

52. Treisman, R.: Regulation of transcription by MAP kinase cascades. Curr. Opinion Cell Biol., 8, 205-215 (1996)

53. Schlessinger, J.: How receptor tyrosine kinases activate Ras. TIBS, 18, 273-275 (1993)

54. Kyriakis, J. M., App, H., Zhang, X.-F., Banerjee, P., Brautigan, D. L., Rapp, U. R. and Avruch, J.: Raf-1 activates MAP kinase-kinase. Nature, 358, 417-421 (1992)

55. Howe, L. R., Leevers, S. J., Gomez, N., Nakielny, S., Cohen, P. and Marshall, C. J.: Activation of the MAP kinase pathway by the protein kinase raf. Cell, 71, 335-342 (1992)

56. Satoh, T., Endo, M., Nakafuku, M., Nakamura, S. and Kaziro, Y.: Platelet-derived growth factor stimulates formation of active p21ras GTP complex in swiss mouse 3T3 cells. Proc. Natl. Acad. Sci. USA., 87, 5993-5997 (1990)

57. Minden, A., Lin, A., McMahon, M., Lange-Carter, C., Derijard, B., Davis, R. J., Johnson, G. L. and Karin, M.: Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science, 266, 1719-1723 (1994)

58. Dent, P., Haser, W., Haystead, T. A., Vicent, L. A., Roberts, T. M. and Sturgill, T. W.: Activation of mitogen-activated protein kinase kinase by v-Raf in 3T3 cells and in vitro. Science, 257, 1404-1407 (1992)

59. Kribben, A., Li, X., Wieder, E. D., Van Putten, V., Schrier, R. W. and Nemenoff, R. A.: AVP-induced activation of MAP kinase in vascular smooth muscle cells is mediated through protein kinase C. Am. J. Physiol., 265, C939-C945 (1993)

60. Takahashi, T., Kawahara, Y., Okuda, M., Ueno, H., Takeshita, A. and Yokoyama, M.: Angiotensin II stimulates mitogen-activated protein kinases and protein synthesis by a Ras-independent pathway in vascular smooth muscle cells. J. Biol. Chem., 272, 16018-16022 (1997)

61. Cowley, S., Paterson, H., Kemp, P. and Marshall, C. J.: Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell, 77, 841-852 (1994)

62. Gille, H., Sharrocks, A. D. and Shaw, P. E.: Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature, 358, 414-417 (1992)

63. Nemenoff, R. A., Winitz, S., Qian, N.-X., Van Putten, V., Johnson, G. L. and Heasley, L. E.: Phosphorylation and activation of a high molecular weight form of phospholipase A2 by p42 MAP kinase and protein kinase C. J. Biol. Chem., 268, 1960-1964 (1993)

64. Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J. and Saltiel, A. R.: A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl. Acad. Sci. USA, 92, 7686-7689 (1995)

65. Coso, O. A., Chiariello, M., Kalinec, G., Kyriakis, J. M., Woodgett, J. and Gutkind, J. S.: Transforming G protein-coupled receptors potently activate JNK(SAPK). J. Biol. Chem., 270, 5620-5624 (1995)

66. Sanchez, I., Hughes, R. T., Mayer, B. J., Yee, K., Woodgett, J. R., Avruch, J., Kyriakis, J. M. and Zon, L. I.: Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature, 372, 794-798 (1994)

67. Shapiro, P. S., Evans, J. N., Davis, R. J. and Posada, J. A.: The seven-transmembrane-spanning receptors for endothelin and thrombin cause proliferation of airway smooth muscle cells and activation of the extracellular regulated kinase and c-Jun NH2-terminal kinase groups of mitogen-activated protein kinases. J. Biol. Chem., 271, 5750-5754 (1996)

68. Minden, A., Lin, A., Claret, F.-X., Abo, A. and Karin, M.: Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell, 81, 1147-1157 (1995)

69. Kyriakis, J. M., Banerjee, P., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J. and Woodgett, J. R.: The stress-activated protein kinase subfamily of c-Jun kinases. Nature, 369, 156-160 (1994)

70. Coso, O. A., Montaner, S., Fromm, C., Lacal, J. C., Prywes, R., Teramoto, H. and Gutkind, J. S.: Signaling from G-protein-coupled receptros to the c-jun promoter involves the MEF2 transcription factor. Evidence for a novel c-jun aminot terminal kinase-independent pathway. J. Biol. Chem., 272, 20691-20697 (1997)

71. Derijard, B., Hibi, M., Wu, I.-H., Barrett, T., Su, B., Deng, T., Karin, M. and Davis, R. J.: JNK1: a protein kinase stimulated by UV light and Ha-ras that binds and phosphorylates the c-Jun activation domain. Cell, 76, 1025-1037 (1994)

72. Kallunki, T., Su, B., Tsigelny, I., Sluss, H. K., Derijard, B., Moore, G., Davis, R. and Karin, M.: JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes Dev., 8, 2996-3007 (1994)

73. Sluss, H. K., Barrett, T., Derijard, B. and Davis, R. J.: Signal transduction by tumor necrosis factor mediated by JNK protein kinases. Mol. Cell. Biol., 14, 8376-8384 (1994)

74. Gupta, S., Barrett, T., Whitmarsh, A. J., Derijard, B. and Davis, R. J.: Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J., 15, 2760-2770 (1996)

75. Whitmarsh, A. J., Shore, P., Sharrocks, A. D. and Davis, R. J.: Integration of MAP kinase signal transduction pathways at the serum response element. Science, 269, 403-407 (1995)

76. Tournier, C., Whitmarsh, A. J., Canavagh, J., Barrett, T. and Davis, R. J.: Miotgen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase. Proc. Natl. Acad. Sci. USA, 94, 7337-7342 (1997)

77. Ruis, H. and Schuller, C.: Stress signaling in yeast. Bioessays, 17, 959-965 (1995)

78. Kramer, R. M., Roberts, E. F., Strifler, B. A. and Johnstone, E. M.: Thrombin induces activation of p38 MAP kinase in human platelets. J. Biol. Chem., 270, 27395-27398 (1995)

79. Lee, J. C., Laydon, J. T., McDonnell, P. C., Gallagher, T. F., Kumar, S., Green, D., McNulty, D., Blumenthal, M. J., Heys, J. R., Landvatter, S. W., Strickler, J. E., McLuaghlin, M. M., Siemens, I. R., Fisher, S. M., Livi, G. P., White, J. R., Adams, J. L. and Young, P. R.: A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature, 372, 739-746 (1994)

80. Schror, K. and Weber, A.-A.: Roles of vasodilatory prostaglandins in mitogenesis of vascular smooth muscle cells. Agents Actions Suppl., 48, 63-91 (1997)

81. Larrue, J., Dorian, B., Daret, D., Demond-Henri, J. and Bricaud, H.: Role of cyclic AMP in the regulation of prostacyclin synthesis by cultured vascular smooth muscle cells. Adv. Cyclic Nucl. Prot. Phosph. Res., 17, 585-592 (1984)

82. Gronich, J. H., Bonventre, J. V. and Nemenoff, R. A.: Purification of Phospholipase A2 from Rat Kidney. Biochem. J., 271, 37-43 (1990)

83. Sharp, J. D., White, D. L., Chiou, X. G., Goodson, T., Gamboa, G. C., McClure, D., Burgett, S., Hoskins, J., Skatrud, P. L., Sportsman, J. R., Becker, G. W., Kang, L. H., Roberts, E. F. and Kramer, R. M.: Molecular cloning and expression of human Ca2+-sensitive cytosolic phospholipase A2. J. Biol. Chem., 266, 14850-14853 (1991)

84. Clark, M. A., Conway, T. M., Shorr, R. G. L. and Crooke, S. T.: Identification and isolation of a mammalian protein which is antigenically and functionally related to the phospholipase A2 stimulatory peptide melittin. J. Biol. Chem., 262, 4402-4406 (1987)

85. Clark, J. D., Milona, N. and Knopf, J. L.: Purification of a 110-kilodalton cytosolic phospholipase A2 from the human monocytic cell line U937. Proc. Natl. Acad. Sci. USA, 87, 7708-7712 (1990)

86. Channon, J. Y. and Leslie, C. C.: A calcium-dependent mechanism for associating a soluble arachidonyl-hydrolyzing phospholipase A2 with membrane in the macrophage cell line RAW 264.7. J. Biol. Chem., 265, 5409-5413 (1990)

87. Glover, S., Bayburt, T., Jonas, M., Chi, E. and Gelb, M. H.: Translocation of the 85-kDa phospholipase A2 from cytosol to the nuclear envelope in rat basophilic leukemia cells stimulated with calcium ionophore or IgE/antigen. J. Biol. Chem., 270, 15359-15367 (1995)

88. Lin, L.-L., Wartmann, M., Lin, A. Y., Knopf, J. L., Seth, A. and Davis, R. J.: cPLA2 is phosphorylated and activated by MAP kinase. Cell, 72, 269-278 (1993)

89. Hazen, S. L., Stuppy, R. J. and Gross, R. W.: Purification and characterization of canine myocardial cytosolic phospholipase A2. J. Biol. Chem., 265, 10622-10630 (1990)

90. Lehman, J. J., Brown, K. A., Ramanadham, S., Turk, J. and Gross, R. W.: Arachidonic acid release from aortic smooth muscle cells induced by [Arg8]vasopressin is largely mediated by calcium-independent phospholipase A2. J. Biol. Chem., 268, 20713-20716 (1993)

91. Wolf, M. J., Wang, J., Turk, J. and Gross, R. W.: Depletion of intracellular calcium stores activates smooth muscle cell calcium-independent phospholipase A2. A novel mechanism underlyign arachidonic acid mobilization. J. Biol. Chem., 272, 1522-1526 (1997)

92. Kujubu, D. A., Fletcher, B. S., Varnum, B. C., Lim, R. W. and Herschman, H. R.: TIS10, a phorbol ester tumor promoter inducible mRNA from Swiss 3T3 cells encodes a novel prostaglandin synthase/cyclooxygenase homologue. J. Biol. Chem., 266, 12866-12872 (1991)

93. Xie, W. and Herschman, H. R.: Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet-derived growth factor and serum. J. Biol. Chem., 271, 31742-31748 (1996)

94. Sasaguri, T., Masuda, J., Shimokado, K., Yokota, T., Kosaka, C., Fujishima, M. and Ogata, J.: Prostaglandins A and J arrest the cell cycle of cultured vascular smooth muscle cells without suppression of c-myc expression. Exp. Cell Res., 200, 351-357 (1992)

95. Anderson, K. M., Roshak, A., Winkler, J. D., McCord, M. and Marshall, L. A.: Cytosolic 85-kDa phospholipase A2-mediated release of arachidonic acid is critical for proliferation of vascular smooth muscle cells. J. Biol. Chem., 272, 30504-30511 (1997)

96. Rao, G. N., Baas, A. S., Glasgow, W. C., Eling, T. E., Runge, M. S. and Alexander, R. W.: Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells. J. Biol. Chem., 269, 32586-32591 (1994)

97. Welsh, C. J., Schmeichel, K., Cao, H. and Chabbott, H.: Vasopressin stimulates phospholipase D activity against phosphatidylcholine in vascular smooth muscle cells. Lipids, 25, 675-684 (1990)

98. Exton, J. H.: Signaling through Phosphatidylcholine Breakdown. J. Biol. Chem., 265, 1-4 (1990)

99. Billah, M. M., Eckel, S., Mullmann, T. J., Egan, R. W. and Siegel, M. I.: Phosphatidylcholine Hydrolysis by Phospholipase D Determines Phosphatidate and Diglyceride Levels in Chemotactic Peptide-stimulated Human Neutrophils. J. Biol. Chem., 264, 17069-17077 (1989)

100. Moolenar, W. H., Kruijer, W., Tilly, B. C., Verlaan, I., Bierman, A. J. and de Laat, S. W.: Growth factor-like action of phosphatidic acid. Nature, 323, 171-173 (1986)

101.van Corven, E. J., Groenink, A., Jalink, K., Eichholtz, T. and Moolenaar, W. H.: Lysophosphatidate-Induced Cell Proliferation: Identification and Dissection of Signaling Pathways Mediated by G proteins. Cell, 59, 45-54 (1989)

102. Sellmayer, A., Uedelhoven, W. M., Weber, P. C. and Bonventre, J. V.: Endogenous Non-cyclooxygenase Metabolites of Arachidonic Acid Modulate Growth and mRNA Levels of Early Response Genes in Rat Mesangial Cells. J. Biol. Chem., 266, 3800-3807 (1991)

103.Thibonnier, M., Bayer, A. L., Simonson, M. S. and Koop, D. R.: V1-vascular AVP receptors of A7r5 cells activate the arachidonic acid cyclooxygenase and epoxygenase pathways. J. Am. Soc. Nephrol., 2, 432 (1991)

104. Hill, C. S. and Treisman, R.: Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell, 80, 199-211 (1994)

105. Treisman, R.: Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J., 6, 2711-2717 (1987)

106. Hill, C. S. and Treisman, R.: Differential regulation of c-fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors. EMBO J., 14, 5037-5047 (1996)

107. Naftilan, A. J., Pratt, R. E. and Dzau, V. J.: Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. J. Clin. Invest., 83, 1419-1424 (1989)

108. Blank, R. S., McQuinn, T. C., Yin, K. C., Thompson, M. M., Takeyasu, K., Schwartz, R. J. and Owens, G. K.: Elements of the smooth muscle a-actin promoter required in cis for transcriptional activation in smooth muscle. J. Biol. Chem., 267, 984-989 (1992)

109. Van Putten, V., Li, X., Maselli, J. and Nemenoff, R. A.: Regulation of smooth muscle-a-actin promoter by vasopressin and PDGF in rat aortic vascular smooth muscle cells. Circ. Res., 75, 1126-1130 (1994)

110. Hautmann, M. B., Thompson, M. M., Swartz, E. A., Olson, E. N. and Owens, G. K.: Angiotensin II-induced stimulation of smooth muscle a-actin expression by serum response factor and the homeodomain transcription factor MHox. Circ. Res., 81, 600-610 (1997)

111. Hautmann, M. B., Madsen, C. S. and Owens, G. K.: A transforming growth factor b (TGFb) control element drives TGFb-induced stimulation of smooth muscle a-actin gene expression in concert with two CArG elements. J. Biol. Chem., 272, 10948-10956 (1997)

112. Muscat, G. E. O., Gustafson, T. A. and Kedes, L.: A common factor regulates skeletal and cardiac a-actin gene transcription in muscle. Mol. Cell. Biol., 8, 4120-4133 (1988)

113. MacLellan, W. r., Lee, T.-C., Schwartz, R. J. and Schneider, M. D.: Transforming growth factor-b response elements of the skeletal a-actin gene. J. Biol. Chem., 269, 16754-16760 (1994)

114. Catala, F., Wanner, R., Barton, P., Cohen, A., Wright, W. and Buckingham, M.: A skeletal muscle-specific enhancer regulated by factors binding to E and CArG boxes is present in the promoter of the mouse mysoin light chain 1A gene. Mol. Cell. Biol., 15, 4585-4596 (1995)

115. Bushel, P., Kim, J. H., Chang, W., Catino, J. J., Ruley, H. E. and Kumar, C. C.: Two serum response elements mediate transcriptional repression of human smooth muscle a-actin promoter in ras-transformed cells. Oncogene, 10, 1361-1370 (1995)

116. Lee, T.-C., Chow, K.-L., Fang, P. and Schwartz, R. J.: Activation of skeletal a-actin gene transcription: the cooperative formation of serum response factor-binding complexes ofver positive cis-acting promoter serum response elements displaces a negative factor enriched in replicating myoblasts and nonmyogenic cells. Mol. Cell. Biol., 11, 5090-5100 (1991)

117. Boxer, L. M., Miwa, T., Gustafson, T. A. and Kedes, L.: Identification and characterization of a factor that binds to two human sarcomeric actin promoters. J. Biol. Chem., 264, 1284-1292 (1989)

118. Shimuzu, R. T., Blank, R. S., Jervis, R., Lawrenz-Smith, S. C. and Owens, G. K.: The smooth muscle a-actin gene promoter is differentially regulated in smooth muscle cells versus non-smooth muscle cells. J. Biol. Chem., 270, 7631-7643 (1995)

119. Paradis, P., MacLellan, W. R., Belaguli, N. S., Schwartz, R. J. and Schneider, M. D.: Serum response factor mediates AP-1-dependent induction of the skeletal a-actin promoter in ventricular myocytes. J. Biol. Chem., 271, 10827-10833 (1996)

120. Groisman, R., Masutani, H., Leibovitch, M.-P., Robin, P., Soudant, I., Trouche, D. and Harel-Bellan, A.: Physical interaction between the mitogen-responsive serum-response factor and myogenic basic-helix-loop-helix proteins. J. Biol. Chem., 271, 5258-5264 (1996)

121. Caramelo, C., Okada, K., Tsai, P. and Schrier, R. W.: Phorbol Esters and arginine vasopressin in vascular smooth muscle cell activation. Am. J. Physiol., 256, F875-F881 (1989)

122. Ganz, M. B., Boyarsky, G., Boron, W. and Sterzel, R. B.: Effects of angiotensin II and vasopressin on intracellular pH of glomerular mesangial cells. Am. J. Physiol., 254, F787-F794 (1988)

123. Mayer, B. and Hemmens, B.: Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem. Sci., 22, 477-481 (1997)

124. Kusano, E., Tian, S., Umino, T., Tetsuka, T., Ando, Y. and Asano, Y.: Arginine vasopressin inhibits interleukin-1 beta-stimulated nitric oxide and cyclic guanosine monophosphate produciton via the V1 receptor in cultured rat vascular smooth muscle cells. J. Hypertens., 15, 627-632 (1997)

125. Yamamoto, K., Ikeda, U., Okada, K., Saito, T. and Shimada, K.: Arginine vasopressin inhibits nitric oxide synthesis in cytokine-stimulated vascular smooth muscle cells. Hypertens. Res., 20, 209-216 (1997)

126. Hamet, P., Hadrava, V., Kruppa, U. and Tremblay, J.: Vascular smooth muscle cell hyperresponsiveness to growth factors in hypertension. J. Hypertens., 6, S36-S39 (1988)

127. Paquet, J. L., Baudoin-Legros, M., Brunelle, G. and Meyer, P.: Angiotensin II-induced proliferation of aortic myocytes in SHR. J. Hypertens., 8, 565-572 (1990)

128. Bendhack, L. M., Sharma, R. V. and Bhalla, R. C.: Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats. Hypertension, 19, II-142-II-148 (1992)

129. Paquet, J.-L., Baudouin-Legros, M., Brunelle, G. and Meyer, P.: Hyperactivation of phospholipase C does not support the enhanced proliferation of aortic smooth muscle cells from spontaneously hypertensive rats. Am. J. Hypertens., 4, 651-660 (1991)

130. Symons, M.: Rho family GTPases: the cytoskeleton and beyond. Trends Biochem. Sci., 21, 178-181 (1996)

131Ridley, A. J. and Hall, A.: The small GTP-binding protein rho regulates the assemblyof focal adhesions and actin stress fibers in response to growth factors. Cell, 70, 389-399 (1992)

132. Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., Iwamatsu, A. and Kaibuchi, K.: Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science, 273, 245-248 (1996)

133. Frid, M. G., Aldashev, A. A., Dempsey, E. C. and Stenmark, K. R.: Smooth muiscle cells isolated from discrete compartments of the mature vascular media exhibit unique phenotypes and distinct growth capabilities. Circ. Res., 81, 940-952 (1997)

Text footnotes:

1. The abbreviations used are: VSMC, vascular smooth muscle cells; MEM, minimal essential media; SM-alpha-actin, smooth muscle- alpha-actin; PCR, polymerase chain reaction; CAT, chloramphenicol acetyl transferase; FCS, fetal calf serum; PAGE, polyacrylaminde gel electrophoresis; PDGF, platelet derived growth factor; PMA, phorbol 12-myristate 13-acetate; AVP, arginine vasopressin; AII, angiotensin II; JNK, cJun NH2-terminal kinase.

2. R.A. Nemenoff, unpublished observations