SLP-76-Cbl-Grb2-Shc interactions in Fcγ/RI signaling

Julie Chu, Yenbou Liu, Gary A. Koretzky, Donald L. Durden

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

SLP-76 and Cbl are complex adapter proteins that have the capacity to bind to smaller adapter proteins, such as Grb2, which subsequently binds the nucleotide exchange protein Sos in the transmission of intracellular signals. SLP-76, Cbl, Shc, and Grb2 have been implicated in immunoreceptor tyrosine- based activation motif (ITAM) signaling, leading to activation of Ras. However, their mechanism of action has not been determined. To date, there have been no reports of SLP-76 involvement in FcγRI-receptor signaling and no data exist for an interaction between Cbl, Shc, and SLP-76 in vivo. We provide evidence that SLP-76, Cbl, and Shc are tyrosine phosphorylated on FcγRI-receptor stimulation and are associated with the adapter protein Grb2 in γ-interferon-differentiated U937 cells (U9371F). The interactions between SLP-76 and Cbl and SLP-76 and Grb2 are present in resting U9371F cells. However, the interaction between SLP-76 and Grb2 becomes augmented twofold on FcγRI-receptor aggregation. Our results provide the first evidence for a phosphorylation-dependent interaction between SLP-76 and Shc, induced at least 10-fold on FcγRI receptor stimulation. Our data indicate that a significant portion of a multimolecular complex containing Cbl, SLP-76, Shc, and Grb2 is distinct from a trimolecular complex containing the Ras guanine nucleotide exchanger Sos, Shc, and Grb2. FcγRI-induced tyrosine phosphorylation of SLP-76, Cbl, Shc, and the highly induced SLP-76-Shc interaction provide the first evidence that SLP-76 and Cbl are involved in FcγRI signaling and suggest a functional significance for these interactions in FcγRI signal relay in the control of Ras in myeloid cells.

Original languageEnglish (US)
Pages (from-to)1697-1706
Number of pages10
JournalBlood
Volume92
Issue number5
Publication statusPublished - Sep 1 1998

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Chu, J., Liu, Y., Koretzky, G. A., & Durden, D. L. (1998). SLP-76-Cbl-Grb2-Shc interactions in Fcγ/RI signaling. Blood, 92(5), 1697-1706.