Role of Src in the modulation of multiple adaptor proteins in FcαRI oxidant signaling

Rae Kil Park, Kayvon D. Izadi, Yashwant M. Deo, Donald L. Durden

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Cross-linking of Fc receptors for IgA, FcαR (CD89), on monocytes/macrophages is known to enhance phagocytic activity and generation of oxygen free radicals. We provide evidence here that the FcαR signals through the γ subunit of FcεRI in U937 cells differentiated with interferon γ (IFNγ). Our results provide the first evidence that FcαR-mediated signals modulate a multimolecular adaptor protein complex containing Grb2, Shc, SHIP, CrkL, Cbl, and SLP-76. Cross-linking of FcαRI using anti-FcαRI induces the phosphorylation of the γ subunit as detected by mobility retardation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Stimulation of FcαRI 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 FcαRI stimulation. The complex adapter proteins, Cbl and SLP-76, are physically associated in myeloid cells and both proteins undergo tyrosine phosphorylation upon FcαR stimulation. These data indicate that the stimulation of FcαR 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 FcαRI-induced production of superoxide anions and provide insight into the mechanism for FcαR- mediated activation of downstream oxidant signaling in myeloid cells.

Original languageEnglish (US)
Pages (from-to)2112-2120
Number of pages9
JournalBlood
Volume94
Issue number6
StatePublished - Sep 15 1999

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Park, R. K., Izadi, K. D., Deo, Y. M., & Durden, D. L. (1999). Role of Src in the modulation of multiple adaptor proteins in FcαRI oxidant signaling. Blood, 94(6), 2112-2120.