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PubMed 21402151


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC3 , TRPC7



Title: Functional regulation of transient receptor potential canonical 7 by cGMP-dependent protein kinase Iα.

Authors: Keizo Yuasa, Taito Matsuda, Akihiko Tsuji

Journal, date & volume: Cell. Signal., 2011 Jul , 23, 1179-87

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21402151


Abstract
The cGMP/cGMP-dependent protein kinase (cGK) signaling pathway is implicated in the functional regulation of intracellular calcium levels. In the present study, we investigated the regulation of transient receptor potential canonical 7 (TRPC7) by the cGMP/cGK-I pathway. TRPC7 contains three putative cGK phosphorylation sites (Arg-Arg/Lys-Xaa-Ser/Thr). However, the role of cGK-I in the regulation of TRPC7 activity remains unclear. In vitro and in vivo kinase assays have revealed that cGK-Iα phosphorylates mouse TRPC7 but not mouse TRPC3. Site-directed mutagenesis analysis revealed that TRPC7 was phosphorylated by cGK-Iα at threonine 15. Phosphorylation of TRPC7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. Furthermore, co-immunoprecipitation assay demonstrated that cGK-Iα interacted with the ankyrin repeat domain in the N terminus of TRPC7. cGK-Iβ also bound to TRPC7, while the type II regulatory subunit of cAMP-dependent protein kinase did not bind. These data indicate that cGK-Iα interacts with and phosphorylates TRPC7, contributing to the quick and accurate regulation of calcium influx and CREB phosphorylation.