Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI).
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 Fc gamma RI aggregation in U937IF cells. Fc gamma RI 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 gamma subunit of Fc gamma RI 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 Fc gamma RI gamma after Fc gamma RI activation and the constitutive association between C3G and Crkl provide the first evidence that a Fc gamma RI gamma-Crkl-C3G complex may link ITAM receptors to the activation of Rap1 in myeloid cells.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Guanine Nucleotide Exchange Factors, Humans, Lymphocyte Activation, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Phosphorylation, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-abl, Proto-Oncogene Proteins c-cbl, Receptor Aggregation, Receptors, IgG, Receptors, Immunologic, Signal Transduction, Tyrosine, U937 Cells, Ubiquitin-Protein Ligases, src Homology Domains
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Guanine Nucleotide Exchange Factors, Humans, Lymphocyte Activation, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Phosphorylation, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-abl, Proto-Oncogene Proteins c-cbl, Receptor Aggregation, Receptors, IgG, Receptors, Immunologic, Signal Transduction, Tyrosine, U937 Cells, Ubiquitin-Protein Ligases, src Homology Domains
J. Immunol.
Date: Nov. 15, 1998
PubMed ID: 9820532
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