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Publication : Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b.

First Author  Zhang W Year  2003
Journal  J Biol Chem Volume  278
Issue  26 Pages  23978-83
PubMed ID  12697763 Mgi Jnum  J:84101
Mgi Id  MGI:2665211 Doi  10.1074/jbc.M212671200
Citation  Zhang W, et al. (2003) Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b. J Biol Chem 278(26):23978-83
abstractText  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.
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