Selective dephosphorylation of the subunits of skeletal muscle calcium channels by purified phosphoprotein phosphatases.
Multiple sites on the alpha 1 and beta subunits of purified skeletal muscle calcium channels are phosphorylated by cyclic AMP-dependent protein kinase, resulting in three different tryptic phosphopeptides derived from each subunit. Phosphoprotein phosphatases dephosphorylated these sites selectively. Phosphoprotein phosphatase 1 (PP1) and phosphoprotein phosphatase 2A (PP2A) dephosphorylated both alpha 1 and beta subunits at similar rates, whereas calcineurin dephosphorylated beta subunits preferentially. PP1 dephosphorylated phosphopeptides 1 and 2 of the alpha 1 subunit more rapidly than phosphopeptide 3. In contrast, PP2A dephosphorylated phosphopeptide 3 of the alpha 1 subunit preferentially. All three phosphoprotein phosphatases preferentially dephosphorylated phosphopeptide 1 of the beta subunit and dephosphorylated phosphopeptides 2 and 3 more slowly. Mn2+ increased the rate and extent of dephosphorylation of all sites by calcineurin so that > 80% dephosphorylation of both alpha 1 and beta subunits was obtained. The results demonstrate selective dephosphorylation of different phosphorylation sites on the alpha 1 and beta subunits of skeletal muscle calcium channels by the three principal serine/threonine phosphoprotein phosphatases.
Lai
Y
Y
Department of Pharmacology, University of Washington, Seattle 98195.
Peterson
B Z
BZ
Catterall
W A
WA
D000818:Animals; D019703:Calcineurin; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D009132:Muscles / Q000378:metabolism*; D010748:Phosphopeptides / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D011817:Rabbits; D014357:Trypsin / Q000494:pharmacology
D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D010748:Phosphopeptides; D008345:Manganese; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D014357:Trypsin