Endogenous Protein Kinase Inhibitors
نویسندگان
چکیده
A thermostable inhibition of ATP:protein phosphotransferase (EC 2.7.1.37) (protein kinase) which is present in crude tissue extracts has been resolved by gel chromatography (Sephadex G-100) into two molecular forms. These two forms will be referred to as type I and type II inhibitor. The type I inhibitor (M, = 24,000) is specific for CAMP-dependent protein kinase and corresponds to the inhibitor described earlier (Walsh, D. A., Ashby, C. D.; Gonzalez, C., Calkins, D., Fisher, E. H., and Krebs, E. G. (1971j.J. Biol. Chem. 246, 1977-1985). The type II inhibitor (3Zr = 15,000) competes for the enzyme with various substrate proteins (histone, a-casein, and Leu-Arg-Arg-Ala-Ser-Leu-Gly (kemptide). The type II inhibitor blocks protein phosphorylation catalyzed by several types of protein kinases (CAMPand cGMP-dependent or cyclic nucleotide-independent protein kinases). The type II inhibitor from rat brain has been purified 1500fold; this protein is thermostable, has acidic characteristics, and does not require Ca’+ ions for its activity. Different ratios and concentrations of type I and type II inhibitors of protein kinase are found in rat skeletal muscle, pancreas, cerebellum and corpus striatum, and in lobster tail muscle.
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