Signal transduction by CXC chemokine receptor 4. Stromal cell-derived factor 1 stimulates prolonged protein kinase B and extracellular signal-regulated kinase 2 activation in T lymphocytes.

@article{citeulike:705818, abstract = {We report that stromal cell-derived factor (SDF)-1 has the remarkable capacity to induce sustained signaling through CXC chemokine receptor 4 (CXCR4). In contrast to other chemokines, such as monocyte chemotactic protein 1 (CC chemokine receptor 2 [CCR2]), macrophage inflammatory protein 1beta (CCR5), liver and activation-regulated chemokine (LARC [CCR6]), Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC [CCR7]), and IP10 (CXCR3), SDF-1 stimulates the prolonged activation of protein kinase B and extracellular signal-regulated kinase (ERK)-2. Activation of protein kinase B is reversed by displacement of SDF-1 from CXCR4 or inhibition of phosphatidylinositol 3-kinase. Although increasing concentrations of SDF-1 enhance CXCR4 internalization, kinase activation is prolonged. In addition, restimulation yields >60\% of initial protein kinase B activity, indicating that the remaining receptors are not desensitized. Furthermore, activation is prolonged by inhibiting SDF-1 degradation. The sustained activation of cell survival and mitogenic pathways may account for the unique role of SDF-1 and CXCR4 in embryogenesis and lymphopoiesis.}, address = {Theodor Kocher-Institute, University of Bern, CH-3000 Bern 9, Switzerland.}, author = {Tilton, B. and Ho, L. and Oberlin, E. and Loetscher, P. and Baleux, F. and Clark-Lewis, I. and Thelen, M. }, citeulike-article-id = {705818}, issn = {0022-1007}, journal = {J Exp Med}, keywords = {cxcr4, tcrmr}, month = {August}, number = {3}, pages = {313--324}, posted-at = {2006-06-23 11:21:34}, priority = {2}, title = {Signal transduction by CXC chemokine receptor 4. Stromal cell-derived factor 1 stimulates prolonged protein kinase B and extracellular signal-regulated kinase 2 activation in T lymphocytes.}, url = {http://www.jem.org/cgi/content/abstract/192/3/313}, volume = {192}, year = {2000} }

TY - JOUR ID - citeulike:705818 L3 - citeulike-article-id:705818 TI - Signal transduction by CXC chemokine receptor 4. Stromal cell-derived factor 1 stimulates prolonged protein kinase B and extracellular signal-regulated kinase 2 activation in T lymphocytes. JF - J Exp Med VL - 192 IS - 3 SP - 313 EP - 324 AD - Theodor Kocher-Institute, University of Bern, CH-3000 Bern 9, Switzerland. SN - 0022-1007 N2 - We report that stromal cell-derived factor (SDF)-1 has the remarkable capacity to induce sustained signaling through CXC chemokine receptor 4 (CXCR4). In contrast to other chemokines, such as monocyte chemotactic protein 1 (CC chemokine receptor 2 [CCR2]), macrophage inflammatory protein 1beta (CCR5), liver and activation-regulated chemokine (LARC [CCR6]), Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC [CCR7]), and IP10 (CXCR3), SDF-1 stimulates the prolonged activation of protein kinase B and extracellular signal-regulated kinase (ERK)-2. Activation of protein kinase B is reversed by displacement of SDF-1 from CXCR4 or inhibition of phosphatidylinositol 3-kinase. Although increasing concentrations of SDF-1 enhance CXCR4 internalization, kinase activation is prolonged. In addition, restimulation yields >60% of initial protein kinase B activity, indicating that the remaining receptors are not desensitized. Furthermore, activation is prolonged by inhibiting SDF-1 degradation. The sustained activation of cell survival and mitogenic pathways may account for the unique role of SDF-1 and CXCR4 in embryogenesis and lymphopoiesis. KW - cxcr4 KW - tcrmr AU - Tilton, B AU - Ho, L AU - Oberlin, E AU - Loetscher, P AU - Baleux, F AU - Clark-Lewis, I AU - Thelen, M PY - 2000/08/07/ UR - http://www.jem.org/cgi/content/abstract/192/3/313 ER -