Physical and functional interaction between calcineurin and the cardiac L-type Ca2+ channel.

ABSTRACT: The L-type Ca(2+) channel (LTCC) is the major mediator of Ca(2+) influx in cardiomyocytes, leading to both mechanical contraction and activation of signaling cascades. Among these Ca(2+)-activated cascades is calcineurin, a protein phosphatase that promotes hypertrophic growth of the heart. Coimmunoprecipitations from heart extracts and pulldowns using heterologously expressed proteins provided evidence for direct binding of calcineurin at both the N and C termini of alpha(1)1.2. At the C terminus, calcineurin bound specifically at amino acids 1943 to 1971, adjacent to a well-characterized protein kinase (PK)A/PKC/PKG phospho-acceptor site Ser1928. In vitro assays demonstrated that calcineurin can dephosphorylate alpha(1)1.2. Channel function was increased in voltage-clamp recordings of I(

SUBMITTER: Tandan S 

PROVIDER: S-EPMC3038593 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature