The FcgammaRII receptor triggers pp125FAK phosphorylation in platelets.
Platelets express a single low affinity receptor for immunoglobulin, FcgammaRII, that triggers multiple cellular responses upon interaction with multivalent immune complexes. In this study we show that immobilized IgG is also a potent stimulant of platelet activation triggering adhesion, aggregation, massive dense granule secretion, and thromboxane production. Platelet adhesion to IgG was blocked by the FcgammaRII receptor-specific monoclonal antibody, IV. 3. Pretreatment of the platelets with cytochalasin D to inhibit actin polymerization similarly prevented cell binding to IgG having no effect on platelet binding to fibrinogen. Platelet adhesion to IgG also led to the induction of tyrosine phosphorylation of multiple proteins including pp125(FAK) and p72(SYK). These proteins were also tyrosine-phosphorylated in alphaIIbbeta3-deficient IgG-adherent platelets from patients with Glanzmann's thrombasthenia. These data demonstrate that FcgammaRII mediates pp125(FAK) phosphorylation and platelet adhesion to IgG independent of the integrin alphaIIbbeta3. Treatment of the platelets with bisindolylmaleimide to inhibit protein kinase C prevented phosphorylation of pp125(FAK) as well as several other proteins, but not p72(SYK) phosphorylation. This study establishes that the FcgammaRII receptor mediates pp125(FAK) phosphorylation via protein kinase C.
Haimovich
B
B
Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
Regan
C
C
DiFazio
L
L
Ginalis
E
E
Ji
P
P
Purohit
U
U
Rowley
R B
RB
Bolen
J
J
Greco
R
R
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000097:blood*; D002614:Chelating Agents / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000097:blood; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D007074:Immunoglobulin G / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008301:Maleimides / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D017452:Receptors, IgG / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D012701:Serotonin / Q000097:blood; D000072377:Syk Kinase; D013929:Thromboxane B2 / Q000097:blood
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D007074:Immunoglobulin G; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D008301:Maleimides; D017452:Receptors, IgG; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D019000:Phosphotyrosine; D012701:Serotonin; D004533:Egtazic Acid; D013929:Thromboxane B2; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase; C088060:bisindolylmaleimide; D007099:Imipramine