title: Mechanism of action of a new component of the Ca(2+)-dependent proteolytic system in rat brain: the calpain activator.
abstract: Rat brain contains a calpain activator specific for the mu-form of the proteinase. We now report that this protein factor binds to the catalytic 80 kDa calpain subunit, promoting the dissociation of the heterodimer structure of the proteinase. The successive steps of the activation process, namely the two autoproteolytic steps producing the 78 kDa and the 75 kDa calpain forms, result in a 100 times faster rate. The activator competes with calpastatin and associates with the inner surface of plasma membranes. Based on its properties, the calpain activator can be visualised as the molecule indicating the sites for calpain activation at which the proteinase can also elude the negative control exerted by calpastatin.
authors.affiliation: Institute of Biological Chemistry, University of Genoa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Melloni
authors.forename: M
authors.initials: M
authors.lastname: Michetti
authors.forename: F
authors.initials: F
authors.lastname: Salamino
authors.forename: B
authors.initials: B
authors.lastname: Sparatore
authors.forename: S
authors.initials: S
authors.lastname: Pontremoli
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D004910:Erythrocyte Membrane / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D011487:Protein Conformation; D051381:Rats
chemical_list: D002135:Calcium-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; C033668:calpastatin; D002154:Calpain; D002118:Calcium