A network of control mediated by of regulator of calcium/calmodulin- dependent signaling

S. V. Rakhilin, P. A. Olson, A. Nishi, N. N. Starkova, A. A. Fienberg, A. C. Nairn*, D. J. Surmeier, P. Greengard

*Corresponding author for this work

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Calmodulin (CaM) is a major effector for the intracellular actions of Ca2+ in nearly all cell types. We identified a CaM-binding protein, designated regulator of calmodulin signaling (RCS). G protein-coupled receptor (GPCR)-dependent activation of protein kinase A (PKA) led to phosphorylation of RCS at Ser55 and increased its binding to CaM. Phospho-RCS acted as a competitive inhibitor of CaM-dependent enzymes, including protein phosphatase 2B (PP2B, also called calcineurin). Increasing RCS phosphorylation blocked GPCR-and PP2B-mediated suppression of L-type Ca2+ currents in striatal neurons. Conversely, genetic deletion of RCS significantly increased this modulation. Through a molecular mechanism that amplifies GPCR- and PKA-mediated signaling and attenuates GPCR- and PP2B-mediated signaling, RCS synergistically increases the phosphorylation of key proteins whose phosphorylation is regulated by PKA and PP2B.

Original languageEnglish (US)
Pages (from-to)698-701
Number of pages4
JournalScience
Volume306
Issue number5696
DOIs
StatePublished - Oct 22 2004

ASJC Scopus subject areas

  • General

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