Role of Src in the Modulation of Multiple Adaptor Proteins in FcRI Oxidant Signaling

Cross-linking of Fc receptors for IgA, FcR (CD89), on monocytes/macrophages is known to enhance phagocytic activity and generation of oxygen free radicals. We provide evidence here that the FcR signals through the γ subunit of FcɛRI in U937 cells differentiated with interferon γ (IFNγ). Our result...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Blood 1999-09, Vol.94 (6), p.2112-2120
Hauptverfasser: Park, Rae-Kil, Izadi, Kayvon D., Deo, Yashwant M., Durden, Donald L.
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Cross-linking of Fc receptors for IgA, FcR (CD89), on monocytes/macrophages is known to enhance phagocytic activity and generation of oxygen free radicals. We provide evidence here that the FcR signals through the γ subunit of FcɛRI in U937 cells differentiated with interferon γ (IFNγ). Our results provide the first evidence that FcR-mediated signals modulate a multimolecular adaptor protein complex containing Grb2, Shc, SHIP, CrkL, Cbl, and SLP-76. Cross-linking of FcRI using anti-FcRI induces the phosphorylation of the γ subunit as detected by mobility retardation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Stimulation of FcRI induced the tyrosine phosphorylation of Shc and increased the association of Grb2 with Shc and CrkL. Grb2 associates constitutively with Sos, and the latter undergoes mobility shift upon FcRI stimulation. The complex adapter proteins, Cbl and SLP-76, are physically associated in myeloid cells and both proteins undergo tyrosine phosphorylation upon FcR stimulation. These data indicate that the stimulation of FcR results in the modulation of adaptor complexes containing tyrosine-phosphorylated Cbl, Shc, SHIP, Grb2, and Crkl. Experiments performed with the Src kinase inhibitor, PP1, provide the first evidence that Src kinase activation is required for FcRI-induced production of superoxide anions and provide insight into the mechanism for FcR-mediated activation of downstream oxidant signaling in myeloid cells.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V94.6.2112