title: The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1.
abstract: Adhesion of T cells after stimulation of the T-cell receptor (TCR) is mediated via signaling processes that have collectively been termed inside-out signaling. The molecular basis for inside-out signaling is not yet completely understood. Here, we show that a signaling module comprising the cytosolic adapter proteins ADAP and SKAP55 is involved in TCR-mediated inside-out signaling and, moreover, that the interaction between ADAP and SKAP55 is mandatory for integrin activation. Disruption of the ADAP/SKAP55 module leads to displacement of the small GTPase Rap1 from the plasma membrane without influencing its GTPase activity. These findings suggest that the ADAP/SKAP55 complex serves to recruit activated Rap1 to the plasma membrane. In line with this hypothesis is the finding that membrane targeting of the ADAP/SKAP55 module induces T-cell adhesion in the absence of TCR-mediated stimuli. However, it appears as if the ADAP/SKAP55 module can exert its signaling function outside of the classical raft fraction of the cell membrane.
authors.affiliation: Institute of Immunology, Otto von Guericke University, 39120 Magdeburg, Germany. stefanie.kliche@medizin.uni-magdeburg.de
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kliche
authors.forename: Dennis
authors.initials: D
authors.lastname: Breitling
authors.forename: Mauro
authors.initials: M
authors.lastname: Togni
authors.forename: Rico
authors.initials: R
authors.lastname: Pusch
authors.forename: Katja
authors.initials: K
authors.lastname: Heuer
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.forename: Christian
authors.initials: C
authors.lastname: Freund
authors.forename: Ana
authors.initials: A
authors.lastname: Kasirer-Friede
authors.forename: Gael
authors.initials: G
authors.lastname: Menasche
authors.forename: Gary A
authors.initials: GA
authors.lastname: Koretzky
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019169:Jurkat Cells; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018821:CD18 Antigens; D005353:Fibronectins; D019012:Integrin beta1; D018799:Intercellular Adhesion Molecule-1; D008565:Membrane Proteins; D010750:Phosphoproteins; D011392:Proline; D011948:Receptors, Antigen, T-Cell; D020827:rap1 GTP-Binding Proteins; C491468:Fyb protein, mouse; C514255:SKAP1 protein, mouse