Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2015 Oct 23

PMID 26491696

Citations 12

Authors

Nobuhiko Satoh

Motonobu Nakamura

Masashi Suzuki

Atsushi Suzuki

George Seki

Shoko Horita

Affiliations

Soon will be listed here.

Abstract

A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2) and stimulates sodium-bicarbonate cotransporter (NBCe1), resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC) and epithelial sodium channel (ENaC) activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK). Moreover, sodium-proton exchanger 3 (NHE3) in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

Citing Articles

Inhibition of Putative Ibrutinib Targets Promotes Atrial Fibrillation, Conduction Blocks, and Proarrhythmic Electrocardiogram Indices: A Mendelian Randomization Analysis.

Xu H, Li B, Lv P, Chen Y, Lin Y, Zhang A Cancer Innov. 2025; 4(2):e70004.

PMID: 40078362 PMC: 11897533. DOI: 10.1002/cai2.70004.

Agomelatine Mitigates Kidney Damage in Obese Insulin-Resistant Rats by Inhibiting Inflammation and Necroptosis via the TNF-α/NF-ĸB/p-RIPK3 Pathway.

Promsan S, Pengrattanachot N, Phengpol N, Sutthasupha P, Thongnak L, Jaikumkao K Int J Mol Sci. 2025; 26(5).

PMID: 40076566 PMC: 11900133. DOI: 10.3390/ijms26051940.

Novel Mutations in Gene in Prostate Cancer Patients in Jordan.

Alasmar A, Al-Alami Z, Zein S, Al-Smadi A, Al Bashir S, Alorjani M Curr Issues Mol Biol. 2024; 46(9):9856-9866.

PMID: 39329938 PMC: 11430622. DOI: 10.3390/cimb46090586.

SGK1 promotes the lipid accumulation via regulating the transcriptional activity of FOXO1 in bovine.

Lei Z, Pan C, Li F, Wei D, Ma Y BMC Genomics. 2024; 25(1):737.

PMID: 39080526 PMC: 11290151. DOI: 10.1186/s12864-024-10644-0.

Apoptosis regulation by the tyrosine-protein kinase CSK.

Fortner A, Chera A, Tanca A, Bucur O Front Cell Dev Biol. 2022; 10:1078180.

PMID: 36578781 PMC: 9792154. DOI: 10.3389/fcell.2022.1078180.

References

Taniguchi C, Emanuelli B, Kahn C . Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol. 2006; 7(2):85-96. DOI: 10.1038/nrm1837. View

Lang F, Perrotti N, Stournaras C . Colorectal carcinoma cells--regulation of survival and growth by SGK1. Int J Biochem Cell Biol. 2010; 42(10):1571-5. DOI: 10.1016/j.biocel.2010.05.016. View

Oki Y, Fanale M, Romaguera J, Fayad L, Fowler N, Copeland A . Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma. Br J Haematol. 2015; 171(4):463-70. PMC: 5278973. DOI: 10.1111/bjh.13603. View

Komers R, Rogers S, Oyama T, Xu B, Yang C, McCormick J . Enhanced phosphorylation of Na(+)-Cl- co-transporter in experimental metabolic syndrome: role of insulin. Clin Sci (Lond). 2012; 123(11):635-47. PMC: 3943429. DOI: 10.1042/CS20120003. View

Fuster D, Bobulescu I, Zhang J, Wade J, Moe O . Characterization of the regulation of renal Na+/H+ exchanger NHE3 by insulin. Am J Physiol Renal Physiol. 2006; 292(2):F577-85. PMC: 2861556. DOI: 10.1152/ajprenal.00240.2006. View

Yoon J, Gilbertson R, Iannaccone S, Iannaccone P, Walterhouse D . Defining a role for Sonic hedgehog pathway activation in desmoplastic medulloblastoma by identifying GLI1 target genes. Int J Cancer. 2008; 124(1):109-19. PMC: 3889649. DOI: 10.1002/ijc.23929. View

Baum M . Insulin stimulates volume absorption in the rabbit proximal convoluted tubule. J Clin Invest. 1987; 79(4):1104-9. PMC: 424290. DOI: 10.1172/JCI112925. View

Cheng C, Huang C . Activation of PI3-kinase stimulates endocytosis of ROMK via Akt1/SGK1-dependent phosphorylation of WNK1. J Am Soc Nephrol. 2011; 22(3):460-71. PMC: 3060440. DOI: 10.1681/ASN.2010060681. View

Cohen Jr M . The AKT genes and their roles in various disorders. Am J Med Genet A. 2013; 161A(12):2931-7. DOI: 10.1002/ajmg.a.36101. View

10.

Nishida H, Sohara E, Nomura N, Chiga M, Alessi D, Rai T . Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice. Hypertension. 2012; 60(4):981-90. PMC: 3743028. DOI: 10.1161/HYPERTENSIONAHA.112.201509. View

11.

Gonzalez E, McGraw T . Insulin signaling diverges into Akt-dependent and -independent signals to regulate the recruitment/docking and the fusion of GLUT4 vesicles to the plasma membrane. Mol Biol Cell. 2006; 17(10):4484-93. PMC: 1635362. DOI: 10.1091/mbc.e06-07-0585. View

12.

Miller T, Rexer B, Garrett J, Arteaga C . Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 2011; 13(6):224. PMC: 3315683. DOI: 10.1186/bcr3039. View

13.

Ishiki M, Klip A . Minireview: recent developments in the regulation of glucose transporter-4 traffic: new signals, locations, and partners. Endocrinology. 2005; 146(12):5071-8. DOI: 10.1210/en.2005-0850. View

14.

Ring A, Leng Q, Rinehart J, Wilson F, Kahle K, Hebert S . An SGK1 site in WNK4 regulates Na+ channel and K+ channel activity and has implications for aldosterone signaling and K+ homeostasis. Proc Natl Acad Sci U S A. 2007; 104(10):4025-9. PMC: 1803763. DOI: 10.1073/pnas.0611728104. View

15.

Webster M, Goya L, Ge Y, Maiyar A, Firestone G . Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol Cell Biol. 1993; 13(4):2031-40. PMC: 359524. DOI: 10.1128/mcb.13.4.2031-2040.1993. View

16.

Chia S, Gandhi S, Joy A, Edwards S, Gorr M, Hopkins S . Novel agents and associated toxicities of inhibitors of the pi3k/Akt/mtor pathway for the treatment of breast cancer. Curr Oncol. 2015; 22(1):33-48. PMC: 4324342. DOI: 10.3747/co.22.2393. View

17.

Hoorn E, Ellison D . WNK kinases and the kidney. Exp Cell Res. 2012; 318(9):1020-6. PMC: 3922210. DOI: 10.1016/j.yexcr.2012.02.029. View

18.

Uchida S . Pathophysiological roles of WNK kinases in the kidney. Pflugers Arch. 2010; 460(4):695-702. DOI: 10.1007/s00424-010-0848-7. View

19.

Sherk A, Frigo D, Schnackenberg C, Bray J, Laping N, Trizna W . Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer Res. 2008; 68(18):7475-83. PMC: 2562281. DOI: 10.1158/0008-5472.CAN-08-1047. View

20.

Albiston A, Yeatman H, Pham V, Fuller S, Diwakarla S, Fernando R . Distinct distribution of GLUT4 and insulin regulated aminopeptidase in the mouse kidney. Regul Pept. 2010; 166(1-3):83-9. DOI: 10.1016/j.regpep.2010.09.003. View