Title | Mammalian brain phosphoproteins as substrates for calcineurin. |
Publication Type | Journal Article |
Year of Publication | 1984 |
Authors | King MM, Huang CY, Chock PB, Nairn AC, Hemmings HC, Chan KF, Greengard P |
Journal | J Biol Chem |
Volume | 259 |
Issue | 13 |
Pagination | 8080-3 |
Date Published | 1984 Jul 10 |
ISSN | 0021-9258 |
Keywords | Animals, Brain, Calmodulin-Binding Proteins, Cattle, Kinetics, Nerve Tissue Proteins, Phosphoprotein Phosphatases, Phosphoproteins, Substrate Specificity |
Abstract | Calcineurin, a Ca2+/calmodulin-dependent phosphoprotein phosphatase found in several tissues, is highly concentrated in mammalian brain. In an attempt to identify endogenous brain substrates for calcineurin, kinetic analyses of the dephosphorylation of several well-characterized phosphoproteins purified from brain were performed. The proteins studied were: G-substrate, a substrate for cyclic GMP-dependent protein kinase; DARPP-32, a substrate for cyclic AMP-dependent protein kinase; Protein K.-F., a substrate for a cyclic nucleotide- and Ca2+-independent protein kinase; and synapsin I, a substrate for cyclic AMP-dependent (site I) and a Ca2+/calmodulin-dependent protein kinase (site II). Calcineurin dephosphorylated each of these proteins in a Ca2+/calmodulin-dependent manner. Similar Km values were obtained for each substrate: G-substrate, 3.8 microM; DARPP-32, 1.6 microM; Protein K.-F., approximately 3 microM (S0.5); synapsin I (site I), 7.0 microM; synapsin I (site II), 4.4 microM. However, significant differences were obtained for the maximal rates of dephosphorylation. The kcat values were: G-substrate, 0.41 s-1; DARPP-32, 0.20 s-1; Protein K.-F., 0.7 s-1; synapsin I (site I), 0.053 s-1; synapsin I (site II), 0.040 s-1. Comparisons of the catalytic efficiency (kcat/Km) for each substrate indicated that DARPP-32, G-substrate, and Protein K.-F. are all potential substrates for calcineurin in vivo. |
Alternate Journal | J. Biol. Chem. |
PubMed ID | 6330098 |
Grant List | MH-17387 / MH / NIMH NIH HHS / United States NS-08440 / NS / NINDS NIH HHS / United States |
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