Src Homology 2-Domain Containing Leukocyte-Specific Phosphoprotein of 76 kDa Is Mandatory for TCR-Mediated Inside-Out Signaling, but Dispensable for CXCR4-Mediated LFA-1 Activation, Adhesion, and Migration of T Cells Export

@article{citeulike:5915756, abstract = {Engagement of the TCR or of chemokine receptors such as CXCR4 induces adhesion and migration of T cells via so-called inside-out signaling pathways. The molecular processes underlying inside-out signaling events are as yet not completely understood. In this study, we show that TCR- and CXCR4-mediated activation of integrins critically depends on the membrane recruitment of the adhesion- and degranulation-promoting adapter protein (ADAP)/Src kinase-associated phosphoprotein of 55 kDa (SKAP55)/Rap1-interacting adapter protein (RIAM)/Rap1 module. We further demonstrate that the Src homology 2 domain containing leukocyte-specific phosphoprotein of 76 kDa (SLP76) is crucial for TCR-mediated inside-out signaling and T cell/APC interaction. Besides facilitating membrane recruitment of ADAP, SKAP55, and RIAM, SLP76 regulates TCR-mediated inside-out signaling by controlling the activation of Rap1 as well as Rac-mediated actin polymerization. Surprisingly, however, SLP76 is not mandatory for CXCR4-mediated inside-out signaling. Indeed, both CXCR4-induced T cell adhesion and migration are not affected by loss of SLP76. Moreover, after CXCR4 stimulation, the ADAP/SKAP55/RIAM/Rap1 module is recruited to the plasma membrane independently of SLP76. Collectively, our data indicate a differential requirement for SLP76 in TCR- vs CXCR4-mediated inside-out signaling pathways regulating T cell adhesion and migration. 10.4049/jimmunol.0900649}, author = {Horn, Jessica and Wang, Xiaoqian and Reichardt, Peter and Stradal, Theresia E. and Warnecke, Nicole and Simeoni, Luca and Gunzer, Matthias and Yablonski, Deborah and Schraven, Burkhart and Kliche, Stefanie}, citeulike-article-id = {5915756}, citeulike-linkout-0 = {http://dx.doi.org/10.4049/jimmunol.0900649}, citeulike-linkout-1 = {http://www.jimmunol.org/cgi/content/abstract/183/9/5756}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19812192}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19812192}, day = {1}, doi = {10.4049/jimmunol.0900649}, issn = {1550-6606}, journal = {J Immunol}, keywords = {adap, rap1, skap55, slp-76}, month = {November}, number = {9}, pages = {5756--5767}, posted-at = {2009-10-09 12:44:50}, priority = {2}, title = {Src Homology 2-Domain Containing Leukocyte-Specific Phosphoprotein of 76 kDa Is Mandatory for TCR-Mediated Inside-Out Signaling, but Dispensable for CXCR4-Mediated LFA-1 Activation, Adhesion, and Migration of T Cells}, url = {http://dx.doi.org/10.4049/jimmunol.0900649}, volume = {183}, year = {2009} }

TY - JOUR ID - citeulike:5915756 L3 - citeulike-article-id:5915756 N2 - Engagement of the TCR or of chemokine receptors such as CXCR4 induces adhesion and migration of T cells via so-called inside-out signaling pathways. The molecular processes underlying inside-out signaling events are as yet not completely understood. In this study, we show that TCR- and CXCR4-mediated activation of integrins critically depends on the membrane recruitment of the adhesion- and degranulation-promoting adapter protein (ADAP)/Src kinase-associated phosphoprotein of 55 kDa (SKAP55)/Rap1-interacting adapter protein (RIAM)/Rap1 module. We further demonstrate that the Src homology 2 domain containing leukocyte-specific phosphoprotein of 76 kDa (SLP76) is crucial for TCR-mediated inside-out signaling and T cell/APC interaction. Besides facilitating membrane recruitment of ADAP, SKAP55, and RIAM, SLP76 regulates TCR-mediated inside-out signaling by controlling the activation of Rap1 as well as Rac-mediated actin polymerization. Surprisingly, however, SLP76 is not mandatory for CXCR4-mediated inside-out signaling. Indeed, both CXCR4-induced T cell adhesion and migration are not affected by loss of SLP76. Moreover, after CXCR4 stimulation, the ADAP/SKAP55/RIAM/Rap1 module is recruited to the plasma membrane independently of SLP76. Collectively, our data indicate a differential requirement for SLP76 in TCR- vs CXCR4-mediated inside-out signaling pathways regulating T cell adhesion and migration. 10.4049/jimmunol.0900649 IS - 9 JF - J Immunol SN - 1550-6606 EP - 5767 TI - Src Homology 2-Domain Containing Leukocyte-Specific Phosphoprotein of 76 kDa Is Mandatory for TCR-Mediated Inside-Out Signaling, but Dispensable for CXCR4-Mediated LFA-1 Activation, Adhesion, and Migration of T Cells VL - 183 SP - 5756 KW - adap KW - rap1 KW - skap55 KW - slp-76 AU - Horn, Jessica AU - Wang, Xiaoqian AU - Reichardt, Peter AU - Stradal, Theresia AU - Warnecke, Nicole AU - Simeoni, Luca AU - Gunzer, Matthias AU - Yablonski, Deborah AU - Schraven, Burkhart AU - Kliche, Stefanie PY - 2009/11/01/ UR - http://dx.doi.org/10.4049/jimmunol.0900649 ER -