Differential interaction of Crkl with Cbl or C3G, Hef-1, and γ subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (FcγRI)

Wade T. Kyono, Ron De Jong, Rae Kil Park, Yenbou Liu, Nora Heisterkamp, John Groffen, Donald L. Durden

Research output: Contribution to journalArticle

19 Scopus citations


Cbl-Crkl and Crkl-C3G interactions have been implicated in T cell and B cell receptor signaling and in the regulation of the small GTPase, Rap1. Recent evidence suggests that Rap1 plays a prominent role in the regulation of immunoreceptor tyrosine-based activation motif (ITAM) signaling. To gain insight into the role of Crkl in myeloid ITAM signaling, we investigated Cbl- Crkl and Crkl-C3G interactions following FcγRI aggregation in U937IF cells. FcγRI cross-linking of U937IF cells results in the tyrosine phosphorylation of Cbl, Crkl, and Hef-1, an increase in the association of Crkl with Cbl via direct SH2 domain interaction and increased Crkl-Hef-1 binding. Crkl constitutively binds to the guanine nucleotide-releasing protein, C3G, via direct SH3 domain binding. Our data show that distinct Cbl-Crkl and Crkl-C3G complexes exist in myeloid cells, suggesting that these complexes may modulate distinct signaling events. Anti-Crkl immunoprecipitations demonstrate that the ITAM-containing γ, subunit of FcγRI is induced to form a complex with the Crkl protein, and Crkl binds to the cytoskeletal protein, Hef-1. The induced association of Crkl with Cbl, Hef-1, and FcγRIγ after FcγRI activation and the constitutive association between C3G and Crkl provide the first evidence that a FcγRIγ-Crkl-C3G complex may link ITAM receptors to the activation of Rap1 in myeloid cells.

Original languageEnglish (US)
Pages (from-to)5555-5563
Number of pages9
JournalJournal of Immunology
Issue number10
Publication statusPublished - Nov 15 1998


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this