The Calpain-Calpastatin System in Hematopoietic Cells

Abstract

Calpain is a Ca²⁺-dependent cysteine endopeptidase [EC 3.4.22. 17] and calpastatin is a calpain-specific endogenous inhibitor protein (Murachi et al., 1981b). At least two molecular species of calpain are known to exist. Calpain I requires low or μM concentration of Ca²⁺ for activation, and calpain II requires high or mM Ca²⁺. Both calpains I and II are heterodimers, each consisting of one heavy (approximately 80 kDa) and one light (approximately 30 kDa) subunits. The heavy subunits of calpains I and II are different genetic products, while the light subunits of both calpains are identical (Murachi, 1983; Suzuki, 1987). Calpastatin is an extremely heat-stable protein, which can be separated from calpains by appropriate chromatographies in the presence of Ca²⁺-chelating agent such as EGTA (ethylene glycol bis(ß-aminoethyl ether)-N,N,N′,N′-tetraactic acid)(Nishiura et al., 1978; Waxman and Krebs, 1978). Calpastatin can bind to and thus inhibit calpain, either I or II, only when the enzyme is activated by Ca²⁺ (Murachi et al., 1981b). Isolation and nucleotide sequencing of cDNAs for several molecular species of calpains and calpastatins have recently been completed, establishing the primary structures of these molecules (Ohno et al., 1984; Sakihama et al., 1985; Takano et al., 1986; Emori et al., 1987; Takano et al., 1988).

This work was supported in part by a grant for Scientific Research from the Ministry of Education, Science and Culture, Japan and a grant for Basic Research from the Muscular Dystrophy Association, U.S.A. (to T.M.)