Protein kinase C-mediated regulation of L-type Ca channels from skeletal muscle requires phosphorylation of the alpha 1 subunit.
Dihydropyridine-sensitive, L-type Ca channels are hetero-oligomeric proteins that are modulated in certain cell types by protein kinase C (PKC). In native skeletal muscle membranes, PKC phosphorylates the alpha 1 and beta subunits of these Ca channels and modulates channel activity. However, it is unknown if phosphorylation of both subunits is necessary for PKC-mediated channel regulation. Here we report that stoichiometric phosphorylation of the alpha 1 subunit was required for activation of these Ca channels by PKC, while PKC-mediated phosphorylation of the beta subunit alone did not modify channel activity. Furthermore, reversal of the functional effects of PKC by protein phosphatase-1c was quantitatively correlated with dephosphorylation of the alpha 1 subunit.
Gutierrez
L M
LM
Department of Molecular Pharmacology & Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611.
Zhao
X L
XL
Hosey
M M
MM
D000818:Animals; D001921:Brain / Q000201:enzymology; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D002645:Chickens; D004095:Dihydropyridines / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism; D046911:Macromolecular Substances; D009132:Muscles / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits
D015220:Calcium Channels; D004095:Dihydropyridines; D008081:Liposomes; D046911:Macromolecular Substances; C038806:1,4-dihydropyridine; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases