IgA Fc receptor (CD89) activation enables coupling to syk and Btk tyrosine kinase pathways: differential signaling after IFN-gamma or phorbol ester stimulation.
IgA Fc receptors (Fc alphaR) can mediate a variety of inflammatory responses. It has been demonstrated that the FcRgamma subunit is critical in mediating signaling through Fc alphaR. We show that aggregation of Fc alphaR on U937 cells and blood neutrophils results in tyrosine phosphorylation of several intracellular proteins, including the FcR gamma subunit, p72syk, and Bruton tyrosine kinase (Btk). Syk was found to be associated with Fc alphaR and its phosphorylation was increased in phorbol myristate acetate (PMA)- and interferon-gamma (IFN-gamma)-treated U937 cells. In contrast, phosphorylation of Btk was only detected after cell treatment with PMA but not IFN-gamma. These data indicate that signaling through Fc alphaR gamma2 involves at least two subfamilies of tyrosine kinases, syk and Btk. Our results also suggest that activation of tyrosine kinase pathways through Fc alphaR depends on the activation state of the cell. This may be an important regulatory mechanism in IgA-mediated responses at inflammatory sites.
Launay
P
P
Institut National de la Santé et de la Recherche Médicale, Unité 25, Hôpital Necker, Paris, France.
Lehuen
A
A
Kawakami
T
T
Blank
U
U
Monteiro
R C
RC
D000077329:Agammaglobulinaemia Tyrosine Kinase; D015703:Antigens, CD / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology*; D015398:Signal Transduction; D000072377:Syk Kinase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D004792:Enzyme Precursors; C036832:Fc(alpha) receptor; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D011961:Receptors, Fc; D019000:Phosphotyrosine; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase; D013755:Tetradecanoylphorbol Acetate