Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion.

@article{Ghandour2007EssentialRF,
  title={Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion.},
  author={Haifa Ghandour and Xavier Culleré and A. Alvarez and Francis W. Luscinskas and Tanya N Mayadas},
  journal={Blood},
  year={2007},
  volume={110 10},
  pages={
          3682-90
        }
}
Regulated adhesion of T cells by the integrins LFA-1 (lymphocyte function-associated antigen-1) and VLA-4 (very late antigen-4) is essential for T-cell trafficking. The small GTPase Rap1 is a critical activator of both integrins in murine lymphocytes and T-cell lines. Here we examined the contribution of the Rap1 regulatory pathway in integrin activation in primary CD3(+) human T cells. We demonstrate that inactivation of Rap1 GTPase in human T cells by expression of SPA1 or Rap1GAP blocked… Expand
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It is suggested that Rap1 determines the functional availability of integrins for productive binding to integrin ligands and that available levels of GTP-bound Rap1 are required for the direct activation of LFA-1 and VLA-4. Expand
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It is demonstrated that phospholipase C (PLC)-γ1 plays a critical role in the signaling pathway leading to Rap1 activation triggered by the TCR, and that TCR activation of Rap1 depends on CalDAG-GEFI, which is likely to activate LFA-1. Expand
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It is indicated that TCR-induced up-regulation of LFA-1-dependent adhesiveness and resulting T cell-APC conjugation require talin1. Expand
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It is indicated that Rap1 GTP is required for the cell adhesion induced by both extracellular matrix and soluble factors, which is negatively regulated by SPA-1. Expand
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The integrin lymphocyte function-associated antigen-1 (LFA-1) expressed on T cells serves as a useful model for analysis of leukocyte integrin functional activity. We have assessed the role ofExpand
Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion
TLDR
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This report identifies Rap1, not RhoA, as a critical geranylgeranylated protein mediating phorbol ester-stimulated β1 and β2integrin-dependent adhesion of Jurkat cells. Expand
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