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Differential Phosphorylation of τ by Cyclic AMP‐Dependent Protein Kinase and Ca 2+ /Calmodulin‐Dependent Protein Kinase II: Metabolic and Functional Consequences
Author(s) -
Johnson Gail V. W.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb10094.x
Subject(s) - phosphorylation , calmodulin , protein kinase a , kinase , protein phosphorylation , chemistry , biochemistry , calpain , phosphopeptide , microbiology and biotechnology , biology , enzyme
The effects of cyclic AMP‐dependent protein kinase (cAMP‐PK) or Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII) phosphorylation on the binding of bovine τ to tubulin and calpain‐mediated degradation of τ were studied. Both cAMP‐PK and CaMKII readily phosphorylated τ and slowed the migration of τ on sodium dodecyl sulfate‐containing polyacrylamide gels. However, cAMP‐PK phosphorylated τ to a significantly greater extent than CaMKII (1.5 and 0.9 mol of 32 P/mol of τ, respectively), and phosphorylation of τ by cAMP‐PK resulted in a greater shift to a more acidic, less heterogeneous pattern on two‐dimensional nonequilibrium pH gradient gels compared with CaMKII phosphorylation. Two‐dimensional phosphopeptide maps indicate that cAMP‐PK phosphorylates a site or sites on τ that are phosphorylated by CaMKII, as well as a unique site or sites that are not phosphorylated by CaMKII. Phosphorylation of τ by cAMP‐PK significantly decreased tubulin binding and, as previously reported, also inhibited the calpain‐induced degradation of τ. CaMKII phosphorylation of τ did not alter either of these parameters. These results suggest that the phosphorylation of site(s) on the τ molecule uniquely accessible to cAMP‐PK contributed to the decreased τ‐tubulin binding and increased resistance to calpain hydrolysis.