Mammalian brain phosphoproteins as substrates for calcineurin.

TitleMammalian brain phosphoproteins as substrates for calcineurin.
Publication TypeJournal Article
Year of Publication1984
AuthorsKing MM, Huang CY, Chock PB, Nairn AC, Hemmings HC, Chan KF, Greengard P
JournalJ Biol Chem
Date Published1984 Jul 10
KeywordsAnimals, Brain, Calmodulin-Binding Proteins, Cattle, Kinetics, Nerve Tissue Proteins, Phosphoprotein Phosphatases, Phosphoproteins, Substrate Specificity

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 JournalJ. Biol. Chem.
PubMed ID6330098
Grant ListMH-17387 / MH / NIMH NIH HHS / United States
NS-08440 / NS / NINDS NIH HHS / United States