Spacial isolation of protein kinase C activation in thrombin stimulated human platelets.
Thrombin stimulation of human platelets is associated with turnover of inositol phospholipids, mobilization of intracellular Ca2+ stores, and activation of protein kinase C. However, within 5 minutes, the thrombin receptor desensitizes, but can be re-coupled to its effectors by stimulation of alpha 2-adrenergic receptors (Crouch and Lapetina, J. Biol. Chem. 263, 3363-3371, 1988). This effect of epinephrine was found to be inhibited by preincubation of platelets with phorbol ester, suggesting that protein kinase C was inhibitory. However, since thrombin also activated protein kinase C and epinephrine was active following thrombin stimulation of platelets, this implied that thrombin activation of protein kinase C may have been spacially isolated near the thrombin receptor and could not inactivate alpha 2-receptor activity. In the present paper, we have tested this possibility, and we present evidence which strongly favours the possibility that protein kinase C activation by receptors induces its local translocation to the cell membrane.
Crouch
M F
MF
Division of Cell Biology, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
Lapetina
E G
EG
D001792:Blood Platelets / Q000201:enzymology*; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000097:blood; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D007211:Indoles; D007700:Kinetics; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010750:Phosphoproteins / Q000097:blood / Q000302:isolation & purification; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011493:Protein Kinase C / Q000097:blood*; D013917:Thrombin / Q000502:physiology*
D001798:Blood Proteins; D004075:Diglycerides; D005456:Fluorescent Dyes; D007211:Indoles; D010750:Phosphoproteins; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; C044295:1,2-dioctanoylglycerol; D015240:Phorbol 12,13-Dibutyrate; C028429:U 44069; D011493:Protein Kinase C; D013917:Thrombin; C048960:indo-1; D002118:Calcium; D004837:Epinephrine