Negative Regulation of T Cell Antigen Receptor-mediated Crk-L-C3G Signaling and Cell Adhesion by Cbl-b
Copyright policy )Negative Regulation of T Cell Antigen Receptor-mediated Crk-L-C3G Signaling and Cell Adhesion by Cbl-b
It was previously reported that Cbl-b associates with Crk-L in Jurkat T cells. However, the physiological significance of such association remains unclear. Here we examined a regulatory role of Cbl-b in Crk-L-C3G signaling pathway. We found that Cbl-b associates with, and induces, ubiquitin conjugation to Crk-L, which requires a functional RING finger. Cbl-b deficiency does not affect Crk-L stability, but its association with C3G. In Cbl-b-/- T cells, the interaction between Crk-L and C3G, and the activity of the small GTPase Rap1, are increased. Cbl-b-/- T cells also display increased adhesion and cell surface binding to ICAM-1, a finding that is supported by the enhanced clustering of LFA-1 in Cbl-b-/- T cells in response to TCR stimulation. Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells.
- La Jolla Institute For Allergy & Immunology United States
Ubiquitin, T-Lymphocytes, Ubiquitin-Protein Ligases, Receptors, Antigen, T-Cell, Nuclear Proteins, rap1 GTP-Binding Proteins, Intercellular Adhesion Molecule-1, Lymphocyte Activation, Phosphoproteins, Lymphocyte Function-Associated Antigen-1, Jurkat Cells, Cell Adhesion, Humans, Proto-Oncogene Proteins c-cbl, Carrier Proteins, Guanine Nucleotide-Releasing Factor 2, Adaptor Proteins, Signal Transducing, Signal Transduction
Ubiquitin, T-Lymphocytes, Ubiquitin-Protein Ligases, Receptors, Antigen, T-Cell, Nuclear Proteins, rap1 GTP-Binding Proteins, Intercellular Adhesion Molecule-1, Lymphocyte Activation, Phosphoproteins, Lymphocyte Function-Associated Antigen-1, Jurkat Cells, Cell Adhesion, Humans, Proto-Oncogene Proteins c-cbl, Carrier Proteins, Guanine Nucleotide-Releasing Factor 2, Adaptor Proteins, Signal Transducing, Signal Transduction
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