title: Protein kinase C regulates the stimulated accumulation of 3-phosphorylated phosphoinositides in platelets.
abstract: We have shown that platelets stimulated with thrombin or guanosine 5'-[gamma-thio]triphosphate (GTP[S]), both of which activate phospholipase C and protein kinase C (PKC), show enhancement of 3-phosphorylated phosphoinositide accumulation (3-PPI). We now report the following. (1) Inhibition of thrombin- or GTP[S]-stimulated PKC by pseudo-substrate peptide (RFARK) added to permeabilized platelets markedly inhibits 3-PPI, whereas the serine/threonine phosphatase inhibitor, okadaic acid, promotes 3-PPI. PKC activity, insufficient in itself for fully activating 3-PPI, appears crucial to receptor and post-receptor stimulation of 3-PPI, even when tyrosine phosphorylation is unimpaired. (2) Alteration of Gi by ADP-ribosylation only slightly affects the stimulation of 3-PPI by thrombin, and activation of the G-protein Gi by adrenaline has no effect on 3-PPI. (3) Inhibition of PKC blocks activated secretion of platelet-derived growth factor (PDGF). However, PDGF cannot promote platelet 3-PPI, and thus cannot account for the inhibitory effects of RFARK on 3-PPI.
authors.affiliation: Department of Biochemistry, University of Vermont College of Medicine, Burlington 05405.
authors.forename: W G
authors.initials: WG
authors.lastname: King
authors.forename: G L
authors.initials: GL
authors.lastname: Kucera
authors.forename: A
authors.initials: A
authors.lastname: Sorisky
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: S E
authors.initials: SE
authors.lastname: Rittenhouse
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D000246:Adenosine Diphosphate Ribose; D019000:Phosphotyrosine; D014443:Tyrosine; D011493:Protein Kinase C