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Sci. STKE, 6 May 2003
Vol. 2003, Issue 181, p. tw180
[DOI: 10.1126/stke.2003.181.tw180]

EDITORS' CHOICE

LEUKOCYTE ADHESION Rap Control

Leukocytes emigrate from the blood stream into tissues during inflammation. In response to chemokines, immune cells roll along the vascular wall until their integrins facilitate firm attachment to adhesion molecules present on the endothelial cell surface. Transmigration then occurs at intercellular junctions. In contrast to their effects on neutrophils, activated chemokine receptors on lymphocytes do not trigger a phosphatidylinositol 3-kinase-dependent signaling cascade, which suggests an alternate signaling route to regulate chemotaxis. Shimonaka et al. report that, instead, the small guanosine triphosphatase (GTPase) Rap1 becomes activated when primary T cells are stimulated with chemokines. Rap1 was required for adhesion between lymphocyte-associated integrins and immobilized, cognate adhesion molecules. Overexpression of RapV12, a constitutively activated form, increased T cell adhesion and stimulated robust migration on either immobilized ligands or cultured endothelial cells, in the absence of exogenous chemokines. Inhibition of heterotrimeric GTP-binding proteins associated with chemokine receptors did not alter these effects of Rap1, nor did the expression of other Ras or Rho-related small GTPases. The results indicate that Rap1 not only controls lymphocyte adhesion but also controls the cell migration machinery.

M. Shimonaka, K. Katagiri, T. Nakayama, N. Fujita, T. Tsuruo, O. Yoshie, T. Kinashi, Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow. J. Cell Biol. 161, 417-427 (2003). [Abstract] [Full Text]

Citation: Rap Control. Sci. STKE 2003, tw180 (2003).



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