Phosphorylation by protein kinase C inactivates an inositol 1,4,5-trisphosphate 3-kinase purified from human platelets.
An inositol 1,4,5-trisphosphate 3-kinase purified from human platelets contains two major components, 53 and 36 kDa polypeptides. Each polypeptide expresses Ca2+/calmodulin-dependent enzymatic activity and is phosphorylated by an unidentified protein kinase in the enzyme preparation. The 36-kDa polypeptide may be further phosphorylated on serine residues by protein kinase C to a stoichiometry of 0.8 mole phosphate per mole of protein. Phosphorylation of the 36-kDa component is correlated with inhibition of the kinase activity; the inhibitory effect is dependent upon Ca2+ and phosphatidylserine/diolein and may be blocked by a selective peptide inhibitor of protein kinase C. Phosphorylation by protein kinase C decreases the Vmax of the enzyme from 160 to 28 nmol/mg/min; the Km (0.76 microM) is not altered. These data suggest that protein kinase C may negatively regulate inositol 1,4,5-trisphosphate 3-kinase activity in the human platelet.
Lin
A N
AN
Department of Pharmacology, University of Alabama, Birmingham 35294.
Barnes
S
S
Wallace
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D002417:Cattle; D005246:Feedback; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010770:Phosphotransferases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor); D011493:Protein Kinase C / Q000378:metabolism*
D015544:Inositol 1,4,5-Trisphosphate; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D011493:Protein Kinase C