Brief Report

The Small GTPase, Rap1, Mediates CD31-induced Integrin Adhesion

Correspondence to: Johannes L. Bos, Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Tel:31 30 2538989 Fax:31 30 2539035 E-mail:j.l.bos{at}med.uu.nl.

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 ß1 (VLA-4) and ß2 (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.

Key Words: guanine nucleotide exchange factor, extravasation, leukocyte function-associated antigen 1, integrin-mediated adhesion, lymphocyte

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Ryu, J., Futai, K., Feliu, M., Weinberg, R., Sheng, M. (2008). Constitutively Active Rap2 Transgenic Mice Display Fewer Dendritic Spines, Reduced Extracellular Signal-Regulated Kinase Signaling, Enhanced Long-Term Depression, and Impaired Spatial Learning and Fear Extinction. J. Neurosci. 28: 8178-8188 [Abstract] [Full Text]  
• Dupuy, A. G., Caron, E. (2008). Integrin-dependent phagocytosis - spreading from microadhesion to new concepts. J. Cell Sci. 121: 1773-1783 [Abstract] [Full Text]  
• Petersen, R. K., Madsen, L., Pedersen, L. M., Hallenborg, P., Hagland, H., Viste, K., Doskeland, S. O., Kristiansen, K. (2008). Cyclic AMP (cAMP)-Mediated Stimulation of Adipocyte Differentiation Requires the Synergistic Action of Epac- and cAMP-Dependent Protein Kinase-Dependent Processes. Mol. Cell. Biol. 28: 3804-3816 [Abstract] [Full Text]  
• Wagner, D. D., Frenette, P. S. (2008). The vessel wall and its interactions. Blood 111: 5271-5281 [Abstract] [Full Text]  
• Mitra, R. S., Goto, M., Lee, J. S., Maldonado, D., Taylor, J. M.G., Pan, Q., Carey, T. E., Bradford, C. R., Prince, M. E., Cordell, K. G., Kirkwood, K. L., D'Silva, N. J. (2008). Rap1GAP Promotes Invasion via Induction of Matrix Metalloproteinase 9 Secretion, Which Is Associated with Poor Survival in Low N-Stage Squamous Cell Carcinoma. Cancer Res. 68: 3959-3969 [Abstract] [Full Text]  
• Severson, E. A., Jiang, L., Ivanov, A. I., Mandell, K. J., Nusrat, A., Parkos, C. A. (2008). Cis-Dimerization Mediates Function of Junctional Adhesion Molecule A. Mol. Biol. Cell 19: 1862-1872 [Abstract] [Full Text]  
• Ulfman, L. H., Kamp, V. M., van Aalst, C. W., Verhagen, L. P., Sanders, M. E., Reedquist, K. A., Buitenhuis, M., Koenderman, L. (2008). Homeostatic Intracellular-Free Ca2+ Is Permissive for Rap1-Mediated Constitutive Activation of {alpha}4 Integrins on Eosinophils. J. Immunol. 180: 5512-5519 [Abstract] [Full Text]  
• Shintani, Y., Fukumoto, Y., Chaika, N., Svoboda, R., Wheelock, M. J., Johnson, K. R. (2008). Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1. J. Cell Biol. 180: 1277-1289 [Abstract] [Full Text]  
• Yarwood, S. J., Borland, G., Sands, W. A., Palmer, T. M. (2008). Identification of CCAAT/Enhancer-binding Proteins as Exchange Protein Activated by cAMP-activated Transcription Factors That Mediate the Induction of the SOCS-3 Gene. J. Biol. Chem. 283: 6843-6853 [Abstract] [Full Text]  
• Wlodarski, M. W., Nearman, Z., Jankowska, A., Babel, N., Powers, J., Leahy, P., Volk, H.-D., Maciejewski, J. P. (2008). Phenotypic differences between healthy effector CTL and leukemic LGL cells support the notion of antigen-triggered clonal transformation in T-LGL leukemia. J. Leukoc. Biol. 83: 589-601 [Abstract] [Full Text]  
• Li, Y., Yan, J., De, P., Chang, H.-C., Yamauchi, A., Christopherson, K. W. II, Paranavitana, N. C., Peng, X., Kim, C., Munugulavadla, V., Kapur, R., Chen, H., Shou, W., Stone, J. C., Kaplan, M. H., Dinauer, M. C., Durden, D. L., Quilliam, L. A. (2007). Rap1a Null Mice Have Altered Myeloid Cell Functions Suggesting Distinct Roles for the Closely Related Rap1a and 1b Proteins. J. Immunol. 179: 8322-8331 [Abstract] [Full Text]  
• Vernon-Wilson, E. F., Aurade, F., Tian, L., Rowe, I. C. M., Shipston, M. J., Savill, J., Brown, S. B. (2007). CD31 delays phagocyte membrane repolarization to promote efficient binding of apoptotic cells. J. Leukoc. Biol. 82: 1278-1288 [Abstract] [Full Text]  
• Bradfield, P. F., Nourshargh, S., Aurrand-Lions, M., Imhof, B. A. (2007). JAM Family and Related Proteins in Leukocyte Migration (Vestweber Series). Arterioscler. Thromb. Vasc. Bio. 27: 2104-2112 [Abstract] [Full Text]  
• Yoshikawa, Y., Satoh, T., Tamura, T., Wei, P., Bilasy, S. E., Edamatsu, H., Aiba, A., Katagiri, K., Kinashi, T., Nakao, K., Kataoka, T. (2007). The M-Ras-RA-GEF-2-Rap1 Pathway Mediates Tumor Necrosis Factor-{alpha} dependent Regulation of Integrin Activation in Splenocytes. Mol. Biol. Cell 18: 2949-2959 [Abstract] [Full Text]  
• Jeong, H.-W., Li, Z., Brown, M. D., Sacks, D. B. (2007). IQGAP1 Binds Rap1 and Modulates Its Activity. J. Biol. Chem. 282: 20752-20762 [Abstract] [Full Text]  
• Pasvolsky, R., Feigelson, S. W., Kilic, S. S., Simon, A. J., Tal-Lapidot, G., Grabovsky, V., Crittenden, J. R., Amariglio, N., Safran, M., Graybiel, A. M., Rechavi, G., Ben-Dor, S., Etzioni, A., Alon, R. (2007). A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets. J. Exp. Med. 204: 1571-1582 [Abstract] [Full Text]  
• Kondo, S., Scheef, E. A., Sheibani, N., Sorenson, C. M. (2007). PECAM-1 isoform-specific regulation of kidney endothelial cell migration and capillary morphogenesis. Am. J. Physiol. Cell Physiol. 292: C2070-C2083 [Abstract] [Full Text]  
• Itoh, M., Nelson, C. M., Myers, C. A., Bissell, M. J. (2007). Rap1 Integrates Tissue Polarity, Lumen Formation, and Tumorigenic Potential in Human Breast Epithelial Cells. Cancer Res. 67: 4759-4766 [Abstract] [Full Text]  
• Dhanjal, T. S., Pendaries, C., Ross, E. A., Larson, M. K., Protty, M. B., Buckley, C. D., Watson, S. P. (2007). A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice. Blood 109: 4237-4244 [Abstract] [Full Text]  
• Lorenowicz, M. J., Fernandez-Borja, M., Hordijk, P. L. (2007). cAMP Signaling in Leukocyte Transendothelial Migration. Arterioscler. Thromb. Vasc. Bio. 27: 1014-1022 [Abstract] [Full Text]  
• Kuijpers, T. W., Bruggen, R. v., Kamerbeek, N., Tool, A. T. J., Hicsonmez, G., Gurgey, A., Karow, A., Verhoeven, A. J., Seeger, K., Sanal, O., Niemeyer, C., Roos, D. (2007). Natural history and early diagnosis of LAD-1/variant syndrome. Blood 109: 3529-3537 [Abstract] [Full Text]  
• Aivatiadou, E., Mattei, E., Ceriani, M., Tilia, L., Berruti, G. (2007). Impaired Fertility and Spermiogenetic Disorders with Loss of Cell Adhesion in Male Mice Expressing an Interfering Rap1 Mutant. Mol. Biol. Cell 18: 1530-1542 [Abstract] [Full Text]  
• Oestreich, E. A., Wang, H., Malik, S., Kaproth-Joslin, K. A., Blaxall, B. C., Kelley, G. G., Dirksen, R. T., Smrcka, A. V. (2007). Epac-mediated Activation of Phospholipase C{epsilon} Plays a Critical Role in beta-Adrenergic Receptor-dependent Enhancement of Ca2+ Mobilization in Cardiac Myocytes. J. Biol. Chem. 282: 5488-5495 [Abstract] [Full Text]  
• Gao, L., Feng, Y., Bowers, R., Becker-Hapak, M., Gardner, J., Council, L., Linette, G., Zhao, H., Cornelius, L. A. (2006). Ras-Associated Protein-1 Regulates Extracellular Signal-Regulated Kinase Activation and Migration in Melanoma Cells: Two Processes Important to Melanoma Tumorigenesis and Metastasis. Cancer Res. 66: 7880-7888 [Abstract] [Full Text]  
• Huelsmann, S., Hepper, C., Marchese, D., Knoll, C., Reuter, R. (2006). The PDZ-GEF Dizzy regulates cell shape of migrating macrophages via Rap1 and integrins in the Drosophila embryo. Development 133: 2915-2924 [Abstract] [Full Text]  
• Bryn, T., Mahic, M., Enserink, J. M., Schwede, F., Aandahl, E. M., Tasken, K. (2006). The Cyclic AMP-Epac1-Rap1 Pathway Is Dissociated from Regulation of Effector Functions in Monocytes but Acquires Immunoregulatory Function in Mature Macrophages.. J. Immunol. 176: 7361-7370 [Abstract] [Full Text]  
• Vernon-Wilson, E. F., Aurade, F., Brown, S. B. (2006). CD31 promotes {beta}1 integrin-dependent engulfment of apoptotic Jurkat T lymphocytes opsonized for phagocytosis by fibronectin. J. Leukoc. Biol. 79: 1260-1267 [Abstract] [Full Text]  
• Kalfa, N., Ecochard, A., Patte, C., Duvillard, P., Audran, F., Pienkowski, C., Thibaud, E., Brauner, R., Lecointre, C., Plantaz, D., Guedj, A.-M., Paris, F., Baldet, P., Lumbroso, S., Sultan, C. (2006). Activating Mutations of the Stimulatory G Protein in Juvenile Ovarian Granulosa Cell Tumors: A New Prognostic Factor?. J. Clin. Endocrinol. Metab. 91: 1842-1847 [Abstract] [Full Text]  
• Brandsma, D., Ulfman, L., Reijneveld, J. C., Bracke, M., Taphoorn, M. J.B., Zwaginga, J. J., Gebbink, M. F.B., de Boer, H., Koenderman, L., Voest, E. E. (2006). Constitutive integrin activation on tumor cells contributes to progression of leptomeningeal metastases. Neuro Oncol 8: 127-136 [Abstract] [Full Text]  
• Bernardi, B., Guidetti, G. F., Campus, F., Crittenden, J. R., Graybiel, A. M., Balduini, C., Torti, M. (2006). The small GTPase Rap1b regulates the cross talk between platelet integrin {alpha}2beta1 and integrin {alpha}IIbbeta3. Blood 107: 2728-2735 [Abstract] [Full Text]  
• Regalado, M. P., Terry-Lorenzo, R. T., Waites, C. L., Garner, C. C., Malenka, R. C. (2006). Transsynaptic signaling by postsynaptic synapse-associated protein 97.. J. Neurosci. 26: 2343-2357 [Abstract] [Full Text]  
• Zhang, Z., Mitra, R. S., Henson, B. S., Datta, N. S., McCauley, L. K., Kumar, P., Lee, J. S.-J., Carey, T. E., D'Silva, N. J. (2006). Rap1GAP Inhibits Tumor Growth in Oropharyngeal Squamous Cell Carcinoma. Am. J. Pathol. 168: 585-596 [Abstract] [Full Text]  
• Duchniewicz, M., Zemojtel, T., Kolanczyk, M., Grossmann, S., Scheele, J. S., Zwartkruis, F. J. T. (2006). Rap1A-Deficient T and B Cells Show Impaired Integrin-Mediated Cell Adhesion. Mol. Cell. Biol. 26: 643-653 [Abstract] [Full Text]  
• Zhang, L., Chenwei, L., Mahmood, R., Golen, K. v., Greenson, J., Li, G., D'Silva, N. J., Li, X., Burant, C. F., Logsdon, C. D., Simeone, D. M. (2006). Identification of a Putative Tumor Suppressor Gene Rap1GAP in Pancreatic Cancer. Cancer Res. 66: 898-906 [Abstract] [Full Text]  
• Falati, S., Patil, S., Gross, P. L., Stapleton, M., Merrill-Skoloff, G., Barrett, N. E., Pixton, K. L., Weiler, H., Cooley, B., Newman, D. K., Newman, P. J., Furie, B. C., Furie, B., Gibbins, J. M. (2006). Platelet PECAM-1 inhibits thrombus formation in vivo. Blood 107: 535-541 [Abstract] [Full Text]  
• Wee, J. L., Jackson, D. E. (2005). The Ig-ITIM superfamily member PECAM-1 regulates the "outside-in" signaling properties of integrin {alpha}IIb{beta}3 in platelets. Blood 106: 3816-3823 [Abstract] [Full Text]  
• Ulfman, L. H., Alblas, J., van Aalst, C. W., Zwaginga, J. J., Koenderman, L. (2005). Differences in Potency of CXC Chemokine Ligand 8-, CC Chemokine Ligand 11-, and C5a-Induced Modulation of Integrin Function on Human Eosinophils. J. Immunol. 175: 6092-6099 [Abstract] [Full Text]  
• Stork, P. J. S., Dillon, T. J. (2005). Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions. Blood 106: 2952-2961 [Abstract] [Full Text]  
• Zhang, Z., Rehmann, H., Price, L. S., Riedl, J., Bos, J. L. (2005). AF6 Negatively Regulates Rap1-induced Cell Adhesion. J. Biol. Chem. 280: 33200-33205 [Abstract] [Full Text]  
• Li, L., Greenwald, R. J., Lafuente, E. M., Tzachanis, D., Berezovskaya, A., Freeman, G. J., Sharpe, A. H., Boussiotis, V. A. (2005). Rap1-GTP Is a Negative Regulator of Th Cell Function and Promotes the Generation of CD4+CD103+ Regulatory T Cells In Vivo. J. Immunol. 175: 3133-3139 [Abstract] [Full Text]  
• Vielkind, S., Gallagher-Gambarelli, M., Gomez, M., Hinton, H. J., Cantrell, D. A. (2005). Integrin Regulation by RhoA in Thymocytes. J. Immunol. 175: 350-357 [Abstract] [Full Text]  
• Garcia-Bernal, D., Wright, N., Sotillo-Mallo, E., Nombela-Arrieta, C., Stein, J. V., Bustelo, X. R., Teixido, J. (2005). Vav1 and Rac Control Chemokine-promoted T Lymphocyte Adhesion Mediated by the Integrin {alpha}4{beta}1. Mol. Biol. Cell 16: 3223-3235 [Abstract] [Full Text]  
• Schultess, J., Danielewski, O., Smolenski, A. P. (2005). Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets. Blood 105: 3185-3192 [Abstract] [Full Text]  
• Murphy, M. M., Zayed, M. A., Evans, A., Parker, C. E., Ataga, K. I., Telen, M. J., Parise, L. V. (2005). Role of Rap1 in promoting sickle red blood cell adhesion to laminin via BCAM/LU. Blood 105: 3322-3329 [Abstract] [Full Text]  
• Mandell, K. J., Babbin, B. A., Nusrat, A., Parkos, C. A. (2005). Junctional Adhesion Molecule 1 Regulates Epithelial Cell Morphology through Effects on {beta}1 Integrins and Rap1 Activity. J. Biol. Chem. 280: 11665-11674 [Abstract] [Full Text]  
• Wittchen, E. S., Worthylake, R. A., Kelly, P., Casey, P. J., Quilliam, L. A., Burridge, K. (2005). Rap1 GTPase Inhibits Leukocyte Transmigration by Promoting Endothelial Barrier Function. J. Biol. Chem. 280: 11675-11682 [Abstract] [Full Text]  
• Fujita, H., Fukuhara, S., Sakurai, A., Yamagishi, A., Kamioka, Y., Nakaoka, Y., Masuda, M., Mochizuki, N. (2005). Local Activation of Rap1 Contributes to Directional Vascular Endothelial Cell Migration Accompanied by Extension of Microtubules on Which RAPL, a Rap1-associating Molecule, Localizes. J. Biol. Chem. 280: 5022-5031 [Abstract] [Full Text]  
• Berkel, W. P.-v., Verheijen, M.H.G., Cuppen, E., Asahina, M., de Rooij, J., Jansen, G., Plasterk, R.H.A., Bos, J. L., Zwartkruis, F.J.T. (2005). Requirement of the Caenorhabditis elegans RapGEF pxf-1 and rap-1 for Epithelial Integrity. Mol. Biol. Cell 16: 106-116 [Abstract] [Full Text]  
• Enserink, J. M., Price, L. S., Methi, T., Mahic, M., Sonnenberg, A., Bos, J. L., Tasken, K. (2004). The cAMP-Epac-Rap1 Pathway Regulates Cell Spreading and Cell Adhesion to Laminin-5 through the {alpha}3{beta}1 Integrin but Not the {alpha}6{beta}4 Integrin. J. Biol. Chem. 279: 44889-44896 [Abstract] [Full Text]  
• Colicelli, J. (2004). Human RAS Superfamily Proteins and Related GTPases. Sci Signal 2004: re13-re13 [Abstract] [Full Text]  
• Price, L. S., Hajdo-Milasinovic, A., Zhao, J., Zwartkruis, F. J. T., Collard, J. G., Bos, J. L. (2004). Rap1 Regulates E-cadherin-mediated Cell-Cell Adhesion. J. Biol. Chem. 279: 35127-35132 [Abstract] [Full Text]  
• Ralston, K. J., Hird, S. L., Zhang, X., Scott, J. L., Jin, B., Thorne, R. F., Berndt, M. C., Boyd, A. W., Burns, G. F. (2004). The LFA-1-associated Molecule PTA-1 (CD226) on T Cells Forms a Dynamic Molecular Complex with Protein 4.1G and Human Discs Large. J. Biol. Chem. 279: 33816-33828 [Abstract] [Full Text]  
• Remans, P. H. J., Gringhuis, S. I., van Laar, J. M., Sanders, M. E., Papendrecht-van der Voort, E. A. M., Zwartkruis, F. J. T., Levarht, E. W. N., Rosas, M., Coffer, P. J., Breedveld, F. C., Bos, J. L., Tak, P. P., Verweij, C. L., Reedquist, K. A. (2004). Rap1 Signaling Is Required for Suppression of Ras-Generated Reactive Oxygen Species and Protection Against Oxidative Stress in T Lymphocytes. J. Immunol. 173: 920-931 [Abstract] [Full Text]  
• Stossi, F., Barnett, D. H., Frasor, J., Komm, B., Lyttle, C. R., Katzenellenbogen, B. S. (2004). Transcriptional Profiling of Estrogen-Regulated Gene Expression via Estrogen Receptor (ER) {alpha} or ER{beta} in Human Osteosarcoma Cells: Distinct and Common Target Genes for These Receptors. Endocrinology 145: 3473-3486 [Abstract] [Full Text]  
• Lova, P., Campus, F., Lombardi, R., Cattaneo, M., Sinigaglia, F., Balduini, C., Torti, M. (2004). Contribution of Protease-activated Receptors 1 and 4 and Glycoprotein Ib-IX-V in the Gi-independent Activation of Platelet Rap1B by Thrombin. J. Biol. Chem. 279: 25299-25306 [Abstract] [Full Text]  
• van Buul, J. D., Hordijk, P. L. (2004). Signaling in Leukocyte Transendothelial Migration. Arterioscler. Thromb. Vasc. Bio. 24: 824-833 [Abstract] [Full Text]  
• McLeod, S. J., Shum, A. J., Lee, R. L., Takei, F., Gold, M. R. (2004). The Rap GTPases Regulate Integrin-mediated Adhesion, Cell Spreading, Actin Polymerization, and Pyk2 Tyrosine Phosphorylation in B Lymphocytes. J. Biol. Chem. 279: 12009-12019 [Abstract] [Full Text]  
• Katagiri, K., Shimonaka, M., Kinashi, T. (2004). Rap1-mediated Lymphocyte Function-associated Antigen-1 Activation by the T Cell Antigen Receptor Is Dependent on Phospholipase C-{gamma}1. J. Biol. Chem. 279: 11875-11881 [Abstract] [Full Text]  
• Prevost, N., Woulfe, D. S., Tognolini, M., Tanaka, T., Jian, W., Fortna, R. R., Jiang, H., Brass, L. F. (2004). Signaling by ephrinB1 and Eph kinases in platelets promotes Rap1 activation, platelet adhesion, and aggregation via effector pathways that do not require phosphorylation of ephrinB1. Blood 103: 1348-1355 [Abstract] [Full Text]  
• Bivona, T. G., Wiener, H. H., Ahearn, I. M., Silletti, J., Chiu, V. K., Philips, M. R. (2004). Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion. J. Cell Biol. 164: 461-470 [Abstract] [Full Text]  
• Kinashi, T., Aker, M., Sokolovsky-Eisenberg, M., Grabovsky, V., Tanaka, C., Shamri, R., Feigelson, S., Etzioni, A., Alon, R. (2004). LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds. Blood 103: 1033-1036 [Abstract] [Full Text]  
• Hattori, M., Minato, N. (2003). Rap1 GTPase: Functions, Regulation, and Malignancy. J Biochem 134: 479-484 [Abstract] [Full Text]  
• Ishida, D., Yang, H., Masuda, K., Uesugi, K., Kawamoto, H., Hattori, M., Minato, N. (2003). Antigen-driven T cell anergy and defective memory T cell response via deregulated Rap1 activation in SPA-1-deficient mice. Proc. Natl. Acad. Sci. USA 100: 10919-10924 [Abstract] [Full Text]  
• Hochbaum, D., Tanos, T., Ribeiro-Neto, F., Altschuler, D., Coso, O. A. (2003). Activation of JNK by Epac Is Independent of Its Activity as a Rap Guanine Nucleotide Exchanger. J. Biol. Chem. 278: 33738-33746 [Abstract] [Full Text]  
• Boettner, B., Harjes, P., Ishimaru, S., Heke, M., Fan, H. Q., Qin, Y., Van Aelst, L., Gaul, U. (2003). The AF-6 Homolog Canoe Acts as a Rap1 Effector During Dorsal Closure of the Drosophila Embryo. Genetics 165: 159-169 [Abstract] [Full Text]  
• Riggins, R. B., Quilliam, L. A., Bouton, A. H. (2003). Synergistic Promotion of c-Src Activation and Cell Migration by Cas and AND-34/BCAR3. J. Biol. Chem. 278: 28264-28273 [Abstract] [Full Text]  
• Murai, K. K., Pasquale, E. B. (2003). `Eph'ective signaling: forward, reverse and crosstalk. J. Cell Sci. 116: 2823-2832 [Abstract] [Full Text]  
• Rehmann, H., Rueppel, A., Bos, J. L., Wittinghofer, A. (2003). Communication between the Regulatory and the Catalytic Region of the cAMP-responsive Guanine Nucleotide Exchange Factor Epac. J. Biol. Chem. 278: 23508-23514 [Abstract] [Full Text]  
• Zhang, W., Shao, Y., Fang, D., Huang, J., Jeon, M.-S., Liu, Y.-C. (2003). Negative Regulation of T Cell Antigen Receptor-mediated Crk-L-C3G Signaling and Cell Adhesion by Cbl-b. J. Biol. Chem. 278: 23978-23983 [Abstract] [Full Text]  
• de Bruyn, K. M. T., Zwartkruis, F. J. T., de Rooij, J., Akkerman, J.-W. N., Bos, J. L. (2003). The Small GTPase Rap1 Is Activated by Turbulence and Is Involved in Integrin {alpha}IIb{beta}3-mediated Cell Adhesion in Human Megakaryocytes. J. Biol. Chem. 278: 22412-22417 [Abstract] [Full Text]  
• Newman, P. J., Newman, D. K. (2003). Signal Transduction Pathways Mediated by PECAM-1: New Roles for an Old Molecule in Platelet and Vascular Cell Biology. Arterioscler. Thromb. Vasc. Bio. 23: 953-964 [Abstract] [Full Text]  
• Tohyama, Y., Katagiri, K., Pardi, R., Lu, C., Springer, T. A., Kinashi, T. (2003). The Critical Cytoplasmic Regions of the {alpha}L/{beta}2 Integrin in Rap1-induced Adhesion and Migration. Mol. Biol. Cell 14: 2570-2582 [Abstract] [Full Text]  
• Shimonaka, M., Katagiri, K., Nakayama, T., Fujita, N., Tsuruo, T., Yoshie, O., Kinashi, T. (2003). Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow. J. Cell Biol. 161: 417-427 [Abstract] [Full Text]  
• Koopman, W. J. H., Bosch, R. R., van Emst-de Vries, S. E., Spaargaren, M., De Pont, J. J. H. H. M., Willems, P. H. G. M. (2003). R-Ras Alters Ca2+ Homeostasis by Increasing the Ca2+ Leak across the Endoplasmic Reticular Membrane. J. Biol. Chem. 278: 13672-13679 [Abstract] [Full Text]  
• Marchuk, D. A., Srinivasan, S., Squire, T. L., Zawistowski, J. S. (2003). Vascular morphogenesis: tales of two syndromes. Hum Mol Genet 12: R97-112 [Abstract] [Full Text]  
• O'Brien, C. D., Lim, P., Sun, J., Albelda, S. M. (2003). PECAM-1-dependent neutrophil transmigration is independent of monolayer PECAM-1 signaling or localization. Blood 101: 2816-2825 [Abstract] [Full Text]  
• Sakakibara, A., Ohba, Y., Kurokawa, K., Matsuda, M., Hattori, S. (2003). Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway-mediated Rap1 activation. J. Cell Sci. 115: 4915-4924 [Abstract] [Full Text]  
• Chaves-Olarte, E., Freer, E., Parra, A., Guzman-Verri, C., Moreno, E., Thelestam, M. (2003). R-Ras Glucosylation and Transient RhoA Activation Determine the Cytopathic Effect Produced by Toxin B Variants from Toxin A-negative Strains of Clostridium difficile. J. Biol. Chem. 278: 7956-7963 [Abstract] [Full Text]  
• Rangarajan, S., Enserink, J. M., Kuiperij, H. B., de Rooij, J., Price, L. S., Schwede, F., Bos, J. L. (2003). Cyclic AMP induces integrin-mediated cell adhesion through Epac and Rap1 upon stimulation of the {beta}2-adrenergic receptor. J. Cell Biol. 160: 487-493 [Abstract] [Full Text]  
• Larson, M. K., Chen, H., Kahn, M. L., Taylor, A. M., Fabre, J.-E., Mortensen, R. M., Conley, P. B., Parise, L. V. (2003). Identification of P2Y12-dependent and -independent mechanisms of glycoprotein VI-mediated Rap1 activation in platelets. Blood 101: 1409-1415 [Abstract] [Full Text]  
• Caron, E. (2003). Cellular functions of the Rap1 GTP-binding protein: a pattern emerges. J. Cell Sci. 116: 435-440 [Abstract] [Full Text]  
• Tasaka, S., Qin, L., Saijo, A., Albelda, S. M., DeLisser, H. M., Doerschuk, C. M. (2003). Platelet Endothelial Cell Adhesion Molecule-1 in Neutrophil Emigration during Acute Bacterial Pneumonia in Mice and Rats. Am. J. Respir. Crit. Care Med. 167: 164-170 [Abstract] [Full Text]  
• Singh, L., Gao, Q., Kumar, A., Gotoh, T., Wazer, D. E., Band, H., Feig, L. A., Band, V. (2002). The High-Risk Human Papillomavirus Type 16 E6 Counters the GAP Function of E6TP1 toward Small Rap G Proteins. J. Virol. 77: 1614-1620 [Abstract] [Full Text]  
• Nagashima, K.-I., Endo, A., Ogita, H., Kawana, A., Yamagishi, A., Kitabatake, A., Matsuda, M., Mochizuki, N. (2002). Adaptor Protein Crk Is Required for Ephrin-B1-induced Membrane Ruffling and Focal Complex Assembly of Human Aortic Endothelial Cells. Mol. Biol. Cell 13: 4231-4242 [Abstract] [Full Text]  
• Shyy, J. Y.-J., Chien, S. (2002). Role of Integrins in Endothelial Mechanosensing of Shear Stress. Circ. Res. 91: 769-775 [Abstract] [Full Text]  
• Liu, L., Schwartz, B. R., Tupper, J., Lin, N., Winn, R. K., Harlan, J. M. (2002). The GTPase Rap1 Regulates Phorbol 12-Myristate 13-Acetate-stimulated but Not Ligand-induced beta 1 Integrin-dependent Leukocyte Adhesion. J. Biol. Chem. 277: 40893-40900 [Abstract] [Full Text]  
• Taher, T. E. I., Tjin, E. P. M., Beuling, E. A., Borst, J., Spaargaren, M., Pals, S. T. (2002). c-Cbl Is Involved in Met Signaling in B Cells and Mediates Hepatocyte Growth Factor-Induced Receptor Ubiquitination. J. Immunol. 169: 3793-3800 [Abstract] [Full Text]  
• Kang, R., Kae, H., Ip, H., Spiegelman, G. B., Weeks, G. (2002). Evidence for a role for the Dictyostelium Rap1 in cell viability and the response to osmotic stress. J. Cell Sci. 115: 3675-3682 [Abstract] [Full Text]  
• de Bruyn, K. M. T., Rangarajan, S., Reedquist, K. A., Figdor, C. G., Bos, J. L. (2002). The Small GTPase Rap1 Is Required for Mn2+- and Antibody-induced LFA-1- and VLA-4-mediated Cell Adhesion. J. Biol. Chem. 277: 29468-29476 [Abstract] [Full Text]  
• Gunel, M., Laurans, M. S. H., Shin, D., DiLuna, M. L., Voorhees, J., Choate, K., Nelson-Williams, C., Lifton, R. P. (2002). KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proc. Natl. Acad. Sci. USA 99: 10677-10682 [Abstract] [Full Text]  
• McLeod, S. J., Li, A. H. Y., Lee, R. L., Burgess, A. E., Gold, M. R. (2002). The Rap GTPases Regulate B Cell Migration Toward the Chemokine Stromal Cell-Derived Factor-1 (CXCL12): Potential Role for Rap2 in Promoting B Cell Migration. J. Immunol. 169: 1365-1371 [Abstract] [Full Text]  
• Prevost, N., Woulfe, D., Tanaka, T., Brass, L. F. (2002). Interactions between Eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred. Proc. Natl. Acad. Sci. USA 99: 9219-9224 [Abstract] [Full Text]  
• Bertoni, A., Tadokoro, S., Eto, K., Pampori, N., Parise, L. V., White, G. C., Shattil, S. J. (2002). Relationships between Rap1b, Affinity Modulation of Integrin alpha IIbbeta 3, and the Actin Cytoskeleton. J. Biol. Chem. 277: 25715-25721 [Abstract] [Full Text]  
• Hughes, P. E., Oertli, B., Hansen, M., Chou, F.-L., Willumsen, B. M., Ginsberg, M. H. (2002). Suppression of Integrin Activation by Activated Ras or Raf Does Not Correlate with Bulk Activation of ERK MAP Kinase. Mol. Biol. Cell 13: 2256-2265 [Abstract] [Full Text]  
• Woulfe, D., Jiang, H., Mortensen, R., Yang, J., Brass, L. F. (2002). Activation of Rap1B by Gi Family Members in Platelets. J. Biol. Chem. 277: 23382-23390 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents