The small GTPase, Rap1, mediates CD31-induced integrin adhesion. Export

@article{citeulike:5058910, abstract = {Integrin-mediated leukocyte adhesion is a critical aspect of leukocyte function that is tightly regulated by diverse stimuli, including chemokines, antigen receptors, and adhesion receptors. How cellular signals from CD31 and other adhesion amplifiers are integrated with those from classical mitogenic stimuli to regulate leukocyte function remains poorly understood. Here, we show that the cytoplasmic tail of CD31, an important integrin adhesion amplifier, propagates signals that induce T cell adhesion via beta1 (VLA-4) and beta2 (LFA-1) integrins. We identify the small GTPase, Rap1, as a critical mediator of this effect. Importantly, CD31 selectively activated the small Ras-related GTPase, Rap1, but not Ras, R-Ras, or Rap2. An activated Rap1 mutant stimulated T lymphocyte adhesion to intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), as did the Rap1 guanine nucleotide exchange factor C3G and a catalytically inactive mutant of RapGAP. Conversely, negative regulators of Rap1 signaling blocked CD31-dependent adhesion. These findings identify a novel important role for Rap1 in regulating ligand-induced cell adhesion and suggest that Rap1 may play a more general role in coordinating adhesion-dependent signals during leukocyte migration and extravasation. Our findings also suggest an alternative mechanism, distinct from interference with Ras-proximal signaling, by which Rap1 might mediate transformation reversion.}, author = {Reedquist, K. A. and Ross, E. and Koop, E. A. and Wolthuis, R. M. and Zwartkruis, F. J. and van Kooyk, Y. and Salmon, M. and Buckley, C. D. and Bos, J. L.}, citeulike-article-id = {5058910}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/10725328}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=10725328}, day = {20}, issn = {0021-9525}, journal = {The Journal of cell biology}, keywords = {cd31, rap1}, month = {March}, number = {6}, pages = {1151--1158}, posted-at = {2009-07-04 23:42:49}, priority = {2}, title = {The small GTPase, Rap1, mediates CD31-induced integrin adhesion.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10725328}, volume = {148}, year = {2000} }

TY - JOUR ID - citeulike:5058910 L3 - citeulike-article-id:5058910 N2 - Integrin-mediated leukocyte adhesion is a critical aspect of leukocyte function that is tightly regulated by diverse stimuli, including chemokines, antigen receptors, and adhesion receptors. How cellular signals from CD31 and other adhesion amplifiers are integrated with those from classical mitogenic stimuli to regulate leukocyte function remains poorly understood. Here, we show that the cytoplasmic tail of CD31, an important integrin adhesion amplifier, propagates signals that induce T cell adhesion via beta1 (VLA-4) and beta2 (LFA-1) integrins. We identify the small GTPase, Rap1, as a critical mediator of this effect. Importantly, CD31 selectively activated the small Ras-related GTPase, Rap1, but not Ras, R-Ras, or Rap2. An activated Rap1 mutant stimulated T lymphocyte adhesion to intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), as did the Rap1 guanine nucleotide exchange factor C3G and a catalytically inactive mutant of RapGAP. Conversely, negative regulators of Rap1 signaling blocked CD31-dependent adhesion. These findings identify a novel important role for Rap1 in regulating ligand-induced cell adhesion and suggest that Rap1 may play a more general role in coordinating adhesion-dependent signals during leukocyte migration and extravasation. Our findings also suggest an alternative mechanism, distinct from interference with Ras-proximal signaling, by which Rap1 might mediate transformation reversion. IS - 6 JF - The Journal of cell biology SN - 0021-9525 EP - 1158 TI - The small GTPase, Rap1, mediates CD31-induced integrin adhesion. VL - 148 SP - 1151 KW - cd31 KW - rap1 AU - Reedquist, KA AU - Ross, E AU - Koop, EA AU - Wolthuis, RM AU - Zwartkruis, FJ AU - van Kooyk, Y AU - Salmon, M AU - Buckley, CD AU - Bos, JL PY - 2000/03/20/ UR - http://view.ncbi.nlm.nih.gov/pubmed/10725328 ER -