Phosphorylation of rat brain calpastatins by protein kinase C.
Calpastatin, the natural inhibitor of calpain, is present in rat brain in multiple forms, having different molecular masses, due to the presence of one (low Mr form) or four (high Mr form) repetitive inhibitory domains. Recombinant and native calpastatin forms are substrates of protein kinase C, which phosphorylates a single serine residue at their N-terminus. Furthermore, both low and high Mr calpastatins are phosphorylated by protein kinase C at the same site. These calpastatin forms are phosphorylated also by protein kinase A, although with a lower efficiency. The incorporation of a phosphate group determines an increase in the concentration of Ca2+ required to induce the formation of the calpain-calpastatin complex. This effect results in a large decrease of the inhibitory efficiency of calpastatins. We suggest that phosphorylation of calpastatin represents a mechanism capable to balance the actual amount of active calpastatin to the level of calpain to be activated.
Averna
M
M
Department of Experimental Medicine, University of Genoa, Italy.
De Tullio
R
R
Salamino
F
F
Melloni
E
E
Pontremoli
S
S
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats
D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010748:Phosphopeptides; C033668:calpastatin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002154:Calpain