Dephosphorylation of tyrosine hydroxylase by brain protein phosphatases: a predominant role for type 2A.
Extracts from rat corpus striatum, or striatal proteins resolved by chromatography on DE-52, were tested for protein phosphatase activity using tyrosine hydroxylase, phosphorylated by cAMP-dependent protein kinase, as substrate. The predominant dephosphorylating activity was independent of divalent cations and was inhibited by low concentrations (100 nM) of okadaic acid, defining the phosphatase as type 2A. Phosphatase type 2C (Mg2+ and Mn2+ stimulated) was evident in the presence of okadaic acid but at a level of approximately 10% of type 2A activity. Phosphatase 2B (Ca2+ and calmodulin dependent) mediated dephosphorylation of tyrosine hydroxylase was not apparent. The dephosphorylation of [32P]-tyrosine hydroxylase was not modulated by tetrahydrobiopterin, ATP, or GTP. These results indicate that tyrosine hydroxylase which has been phosphorylated by cAMP dependent protein kinase is dephosphorylated predominantly by phosphatase type 2A in brain, and the activity of this phosphatase is not modulated by pteridines or nucleotides.
Berresheim
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Department of Psychiatry, Wayne State University School of Medicine Detroit, Michigan.
Kuhn
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DM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D002852:Chromatography, Ion Exchange; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D017072:Neostriatum / Q000201:enzymology; D019319:Okadaic Acid; D016716:PC12 Cells; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D004988:Ethers, Cyclic; D007527:Isoenzymes; D019319:Okadaic Acid; D001708:Biopterins; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D014446:Tyrosine 3-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; C003402:sapropterin; D004298:Dopamine