GTP and GDP will stimulate platelet cytosolic phospholipase C independently of Ca2+.
The hydrolysis of [3H]phosphatidylinositol 4,5-bisphosphate (PIP2) by cytosolic phospholipase C from human platelets was determined. Cytosolic fractions were prepared from platelets that had or had not been preactivated with thrombin. Thrombin pretreatment did not affect cytosolic phospholipase C activity. In both cytosolic fractions, phospholipase C was activated by GTP and GTP gamma S. This action is observed in the presence of 2 mM EGTA. GDP was as effective as GTP in stimulating cytosolic phospholipase C in the presence of Ca2+ or EGTA. Partially purified phospholipase C obtained from platelet cytosol is activated by GTP, but not by GTP gamma S, in the presence of 2 mM EGTA. However, in the presence of 6 microM Ca2+, both GTP and GTP gamma S stimulated the partially purified phospholipase C. Our present information indicates that GTP and GDP have a direct effect on the cytosolic phospholipase C.
D001792:Blood Platelets / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology*; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006150:Guanine Nucleotides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D013873:Thionucleotides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000097:blood*
D006150:Guanine Nucleotides; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004533:Egtazic Acid; D006160:Guanosine Triphosphate; D010738:Type C Phospholipases; D002118:Calcium