Phospholipase A2 enzymes regulate alpha IIb beta3-mediated, but not Fc gammaRII receptor-mediated, pp125FAK phosphorylation in platelets.
The alphaII(b)beta3 integrin and FcgammaRII receptors mediate, respectively, platelet adhesion and spreading on fibrinogen and immunoglobulin (IgG) coated surfaces. Platelet adhesion to fibrinogen resulted in a partial conversion of the faster to the slower migrating (phosphorylated) form of Ca(+2)-sensitive cytosolic phospholipase A2(cPLA2) but failed to trigger arachidonic acid (AA) release. Full mobility shift of cPLA2 and a massive release of AA release were stimulated by platelet adhesion to IgG or addition of thrombin to the fibrinogen adherent platelets. IgG and thrombin induced AA production were blocked by methyl arachidonyl fluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and the Ca(+2)-independent phospholipase A2 (iPLA2). In contrast, bromoenol lactone (BEL), a specific inhibitor of iPLA2 had no effect on the release of AA. MAFP and BEL prevented pp125FAK phosphorylation and platelet spreading on fibrinogen having no effect on pp125FAK phosphorylation or platelet spreading on immobilized IgG. We conclude that alpha(IIb)beta3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are regulated by PLA2 enzymes.
Haimovich
B
B
Department of Surgery, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. haimovic@umdnj.edu
Ji
P
P
Ginalis
E
E
Kramer
R
R
Greco
R
R
D016718:Arachidonic Acid / Q000096:biosynthesis; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000097:blood*; D005340:Fibrinogen / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D010766:Phosphorylation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D011753:Pyrones / Q000494:pharmacology; D017452:Receptors, IgG / Q000502:physiology*
D001095:Arachidonic Acids; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D009281:Naphthalenes; D063065:Organophosphonates; D010726:Phosphodiesterase Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011753:Pyrones; D017452:Receptors, IgG; C104810:methyl arachidonylfluorophosphonate; D016718:Arachidonic Acid; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D005340:Fibrinogen; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D010741:Phospholipases A; D054467:Phospholipases A2