Release of Ca2+ by inositol 1,4,5-trisphosphate in platelet membrane vesicles is not dependent on cyclic AMP-dependent protein kinase.
In contrast with previous reports, it was found that membrane-protein phosphorylation by the catalytic subunit (CS) of cyclic AMP-dependent protein kinase had no effect on Ca2+ uptake into platelet membrane vesicles or on subsequent Ca2+ release by inositol 1,4,5-trisphosphate (IP3). Furthermore, IP-20, a highly potent synthetic peptide inhibitor of CS, which totally abolished membrane protein phosphorylation by endogenous or exogenous CS, also had no effect on either Ca2+ uptake or release by IP3. Commercial preparations of protein kinase inhibitor protein (PKI) usually had no effect, but one preparation partially inhibited Ca2+ uptake, which is attributable to the gross impurity of the commercial PKI preparation. IP3-induced release of Ca2+ was also unaffected by the absence of ATP from the medium, supporting the conclusion that Ca2+ release by IP3 does not require the phosphorylation of membrane protein.
O'Rourke
F
F
Department of Pharmacology, University of Connecticut Health Center, Farmington 06032.
Zavoico
G B
GB
Feinstein
M B
MB
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013403:Sugar Phosphates / Q000378:metabolism*
D002352:Carrier Proteins; D007295:Inositol Phosphates; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D013403:Sugar Phosphates; C015482:protein kinase modulator; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; C058824:IP 20; D011494:Protein Kinases; D002118:Calcium