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CCT and CCT-Like Modular Protein Interaction Domains in WNK Signaling by Clinton A. Taylor; Melanie H. Cobb is a scholarly article available to read on EtoBox.

What is CCT and CCT-Like Modular Protein Interaction Domains in WNK Signaling about?

The WNK [with no lysine (K)] kinases and their downstream effector kinases, oxidative stress responsive 1 (OSR1) and SPS/STE20-related proline-alanine-rich kinase (SPAK), have well established functions in the maintenance of cell volume and ion homeostasis. Mutations in these kinases have been linked to an inherited form of hypertension, neurologic defects, and other pathologies. A rapidly expanding body of evidence points to the involvement of WNKs in regulating multiple diverse cellular processes as well as the progression of some forms of cancer. How OSR1 and SPAK contribute to these processes is well understood in some cases but completely unknown in others. OSR1 and SPAK are targeted to both WNKs and substrates via their conserved C-terminal (CCT) protein interaction domains. Considerable effort has been put forth to understand the structure, function, and interaction specificity of the CCT domains in relation to WNK signaling, and multiple inhibitors of WNK signaling target these domains. The domains bind RFxV and RxFxV protein sequence motifs with the consensus sequence R-F-x-V/I or R-x-F-x-V/I, but residues outside the core motif also contribute to specificity. CCT interact

Author

Clinton A. Taylor; Melanie H. Cobb

Publisher

American Society for Pharmacology & Experimental Therapeutics (ASPET)

Published

2021

Language

EN