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gaoshandian1金虫 (小有名气)
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Vav1 和 Rac 通过粘合素α4β1控制趋化因子促进的T淋巴细胞黏附
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Control Chemokine-promoted T Lymphocyte Adhesion Mediated by the Integrin David García-Bernal *, Natalia Wright *, Elena Sotillo-Mallo et al The chemokine CXCL12 promotes T lymphocyte adhesion mediated by the integrin α4β1. CXCL12 activates the GTPase Rac, as well as Vav1, a guanine-nucleotide exchange factor for Rac, concomitant with up-regulation of α4β1 -dependent adhesion. Inhibition of CXCL12-promoted Rac and Vav1 activation by transfection of dominant negative Rac or Vav1 forms, or by transfection of their siRNA, remarkably impaired the increase in T lymphocyte attachment to α4β1 ligands in response to this chemokine. Importantly, inhibition of Vav1 expression by RNA interference resulted in a blockade of Rac activation in response to CXCL12. Adhesions in flow chambers and soluble binding assays using these transfectants indicated that initial ligand binding and adhesion strengthening mediated by α4β1 were dependent on Vav1 and Rac activation by CXCL12. Finally, CXCL12-promoted T-cell transendothelial migration involving α4β1 -mediated adhesion was notably inhibited by expression of dominant negative Vav1 and Rac. These results indicate that activation of Vav1-Rac signaling pathway by CXCL12 represents an important inside-out event controlling efficient up-regulation of α4β1 -dependent T lymphocyte adhesion. －－－－－－－－－－－－－－－ MBC Vol. 16, Issue 7, 3223-3235 全文链接 |
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