Identification and characterization of alternative STK39 transcripts within human and mouse kidneys reveals species-specific regulation of blood pressure.

ABSTRACT: STK39 encodes a serine threonine kinase, SPAK, which is part of a multi-kinase network that determines renal Na⁺ reabsorption and blood pressure (BP) through regulation of sodium-chloride co-transporters in the kidney. Variants within STK39 are associated with susceptibility to essential hypertension, and constitutively active SPAK mice are hypertensive and hyperkalemic, similar to familial hyperkalemic hyperkalemia in humans. SPAK null mice are hypotensive and mimic Gitelman syndrome, a rare monogenic salt wasting human disorder. Mice exhibit nephron segment-specific expression of full length SPAK and N-terminally truncated SPAK isoforms (SPAK2 and KS-SPAK) with impaired kinase function. SPAK2 and KS-SPAK function to inhibit phosphorylation of cation co-transporters by full len

SUBMITTER: Mercado CJ 

PROVIDER: S-EPMC7048380 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature