[Frontiers in Bioscience, Landmark, 25, 1386-1411, March 1, 2020]

Protein kinases as regulators of osmolyte accumulation under stress conditions: An overview

Usma Manzoor1, Tanveer A. Dar1

1Clinical Biochemistry, University of Kashmir, Hazratbal, Srinagar, Jammu and Kashmir, 190006

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Osmolyte accumulation - an adaptive response against stress
4. Regulation of osmolyte accumulation
    4.1. At transcriptional level- expression of osmolyte transporter
    4.2. At translational level - Role of protein kinases
      4.2.1. Taurine transporter
      4.2.2. Myoinositol transporter
      4.2.3. Betaine transporter
5. Protein kinases as therapeutic targets
6. Regulation of protein kinases by osmolytes under in vitro conditions
7. Conclusion
8. Future perspectives
9. Acknowledgments
10. References

1. ABSTRACT

Accumulation of osmolytes, during cell volume perturbations, as cell volume regulators is ensured through their de novo synthesis, decreased degradation and transport from their site of synthesis to the site of utility through various transport systems. Among these, transport system mediated accumulation has been observed to be quite significant during long term cell volume perturbation. Under stress conditions, these osmolyte transporters are regulated at transcriptional as well as translational level. At translational level, protein kinases carry out phosphorylation of osmolyte transporters and have been shown to play a crucial role in cell volume homeostasis. In fact phosphorylation of osmolyte transporters on their conserved residues regulates the uptake and efflux of osmolytes by cells. Additionally, accumulated osmolytes in turn have been shown to modulate the structure and functioning of protein kinases. The present review has tried to provide an overview about the role of protein kinases in regulation of osmolyte accumulation under stress conditions. Due to their ability of regulating osmolyte accumulation, potential of protein kinases as therapeutic targets for diseases like cancer has also been highlighted.

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Abbreviations: TonEBP, Tonicity enhancer binding protein; TonE, Tonicity enhancer; RER, Rough endoplasmic reticulum; PKC, Protein kinase C; PKA, Protein kinase A; JAK2, Janus kinase 2; SMIT, Sodium myoinositol transporter; TauT, Taurine transporter; BGT1, Betaine transporter; RPE, Retinal pigment epithelium; HMIT, H+ Myoinositol transporter; NF-kB, Nuclear factor kappa-light-chain-enhancer of activated B cells; TMAO, trimethylamine -N-oxide; CK, creatine kinase; AK, arginine kinase, TM, transmembrane; CK2, casein kinase 2; MDCK, Madin-Darby canine kidney; PDZ, post synaptic density protein(PSD95), drosophila disc large tumor suppressor(Dlg1) and zonula occludens-1 protein(Zo-1)

Key Words: Osmolyte, Protein kinase, Cell volume regulation, Osmolyte transporter, Cancer, Phosphorylation, betaine transporter, taurine transporter, myoinositol transporter

Send correspondence to: Tanveer Ali Dar, Clinical Biochemistry, University of Kashmir, Hazratbal, Srinagar, 190006, Tel: 91-9419639396, Fax: 91-194-227-2096, E-mail: tanveerali@kashmiruniversity.ac.in