The alpha 1-subunit of skeletal muscle L-type Ca channels is the key target for regulation by A-kinase and protein phosphatase-1C.
Despite the fact that the phosphorylation-mediated regulation of L-type Ca channels is viewed as a model of ion channel regulation, much remains to be learned about the protein phosphorylation and dephosphorylation reactions that underlie the regulation of the channels. The channel isoform most well studied biochemically is that expressed in skeletal muscle. The alpha 1- and beta-subunits of this channel isoform are substrates for protein kinase A, but it is unknown if phosphorylation or dephosphorylation of both subunits contributes to altered channel properties. Here, we report experiments in which the alpha 1- and beta-subunits were differentially phosphorylated by protein kinase A and dephosphorylated by protein phosphatase 1c under conditions that led to channel regulation. The results suggest that the alpha 1-subunit plays a key role in the phosphorylation and dephosphorylation-dependent regulation of the L-type Ca channels from skeletal muscle.
Zhao
X L
XL
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Gutierrez
L M
LM
Chang
C F
CF
Hosey
M M
MM
D000818:Animals; D015220:Calcium Channels / Q000302:isolation & purification / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D007700:Kinetics; D046911:Macromolecular Substances; D009132:Muscles / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000302:isolation & purification; D010749:Phosphoprotein Phosphatases / Q000302:isolation & purification / Q000378:metabolism*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D013379:Substrate Specificity
D015220:Calcium Channels; D046911:Macromolecular Substances; D010748:Phosphopeptides; D010750:Phosphoproteins; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases