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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Carrier Proteins, Cell Adhesion, Guanine Nucleotide-Releasing Factor 2, Humans, Intercellular Adhesion Molecule-1, Jurkat Cells, Lymphocyte Activation, Lymphocyte Function-Associated Antigen-1, Nuclear Proteins, Phosphoproteins, Proto-Oncogene Proteins c-cbl, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Ubiquitin, Ubiquitin-Protein Ligases, rap1 GTP-Binding Proteins
Adaptor Proteins, Signal Transducing, Carrier Proteins, Cell Adhesion, Guanine Nucleotide-Releasing Factor 2, Humans, Intercellular Adhesion Molecule-1, Jurkat Cells, Lymphocyte Activation, Lymphocyte Function-Associated Antigen-1, Nuclear Proteins, Phosphoproteins, Proto-Oncogene Proteins c-cbl, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Ubiquitin, Ubiquitin-Protein Ligases, rap1 GTP-Binding Proteins
J. Biol. Chem.
Date: Jun. 27, 2003
PubMed ID: 12697763
View in: Pubmed Google Scholar
Download Curated Data For This Publication
140077
Switch View:
- Interactions 4
- PTM Genes 2