title: Differential proteolysis of the full-length form of the L-type calcium channel alpha 1 subunit by calpain.
abstract: This study examines the proteolysis of the carboxy terminal domain of the full-length (alpha 1(212)) and truncated (alpha 1(190)) forms of the rabbit skeletal muscle L-type calcium channel alpha 1 subunit by calpain I and calpain II. Although both forms of the alpha 1 subunit show little sensitivity to proteolysis by calpain II, alpha 1(212) is relatively more sensitive than alpha 1(190) to digestion by calpain I, the form of the enzyme regulated by micromolar concentrations of calcium. Calpain I cleaves a 37-kDa fragment from the C-terminus of alpha 1(212) in a time- and concentration-dependent manner and proteolysis is independent of the alpha 1(212) phosphorylation state. This proteolytic cleavage removes the major site of cyclic AMP-dependent phosphorylation from alpha 1(212) and may provide a mechanism for modifying the cyclic AMP-dependent regulation of L-type calcium channels in skeletal muscle.
authors.affiliation: Department of Pharmacology, University of Washington, Seattle 98195.
authors.forename: K S
authors.initials: KS
authors.lastname: De Jongh
authors.forename: A A
authors.initials: AA
authors.lastname: Colvin
authors.forename: K K
authors.initials: KK
authors.lastname: Wang
authors.forename: W A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D002154:Calpain / Q000097:blood* / Q000302:isolation & purification; D002846:Chromatography, Affinity; D002848:Chromatography, DEAE-Cellulose; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010446:Peptide Fragments / Q000302:isolation & purification; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D011817:Rabbits
chemical_list: D015220:Calcium Channels; D010446:Peptide Fragments; D010748:Phosphopeptides; D017868:Cyclic AMP-Dependent Protein Kinases; D002154:Calpain