Voltage-dependent potentiation of skeletal muscle L-type calcium channels requires phosphorylation by cAMP-dependent protein kinase (PKA) that is localized by binding to a cAMP-dependent protein kinase-anchoring protein (AKAP). L-type calcium channels purified from rabbit skeletal muscle contain an endogenous co-purifying protein kinase activity that phosphorylates the alpha1 and beta subunits of the channel. The co-purifying kinase also phosphorylates a known PKA peptide substrate, is stimulated by cAMP, and is inhibited by PKA inhibitor peptide-(5-24), indicating that it is PKA. PKA activity co-immunoprecipitates with the calcium channel, suggesting that the channel and the kinase are physically associated. Using biotinylated type II regulatory subunit of PKA (RII) as a probe, we have identified a 15-kDa RII-binding protein in purified calcium channel preparations, which we have designated AKAP-15. Anti-peptide antibodies directed against the alpha1 subunit of the calcium channel co-immunoprecipitate AKAP-15. Together, these findings demonstrate a physical link between PKA and the calcium channel and suggest that AKAP-15 may mediate their interaction.
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