Identification of protein phosphatase 2A as the major tyrosine hydroxylase phosphatase in adrenal medulla and corpus striatum: evidence from the effects of okadaic acid.
(i) The major sites on bovine adrenal tyrosine hydroxylase (TH) phosphorylated by calmodulin-dependent multiprotein kinase (CaM-MPK) and cyclic AMP-dependent protein kinase were shown to be Ser-19 and Ser-40, respectively, while Ser-40 was also phosphorylated slowly by CaM-MPK. (ii) Type 2A and type 2C phosphatases accounted for approximately 90% and approximately 10% of TH phosphatase activity, respectively, in extracts of adrenal medulla and corpus striatum assayed at near physiological free Mg2+ (1 mM), while type 1 and type 2B phosphatases had negligible activity towards TH. (iii) Incubation of adrenal chromaffin cells with okadaic acid increased TH phosphorylation by 206% and activity by 77%, establishing that type 2A phosphatases play a major role in regulating TH in vivo.
Haavik
J
J
Department of Biochemistry, University of Bergen, Norway.
Schelling
D L
DL
Campbell
D G
DG
Andersson
K K
KK
Flatmark
T
T
Cohen
P
P
D000313:Adrenal Medulla / Q000201:enzymology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002417:Cattle; D002838:Chromaffin System / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology*; D004533:Egtazic Acid / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2; D011817:Rabbits; D051381:Rats; D014268:Trifluoperazine / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D004988:Ethers, Cyclic; D047428:Protein Kinase Inhibitors; D019319:Okadaic Acid; D014268:Trifluoperazine; D004533:Egtazic Acid; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D008274:Magnesium