Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.

ABSTRACT: The role of Cl^- as an intracellular signaling ion has been increasingly recognized in recent years. One of the currently best described roles of Cl^- in signaling is the modulation of the With-No-Lysine (K) (WNK) - STE20-Proline Alanine rich Kinase (SPAK)/Oxidative Stress Responsive Kinase 1 (OSR1) - Cation-Coupled Cl^- Cotransporters (CCCs) cascade. Binding of a Cl^- anion to the active site of WNK kinases directly modulates their activity, promoting their inhibition. WNK activation due to Cl^- release from the binding site leads to phosphorylation and activation of SPAK/OSR1, which in turn phosphorylate the CCCs. Phosphorylation by WNKs-SPAK/OSR1 of the Na⁺-driven CCCs (mediating ions influx) promote their activation, whereas

SUBMITTER: Murillo-de-Ozores AR 

PROVIDER: S-EPMC7606576 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature