The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1.
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.
Kliche
Stefanie
S
Institute of Immunology, Otto von Guericke University, 39120 Magdeburg, Germany. stefanie.kliche@medizin.uni-magdeburg.de
Breitling
Dennis
D
Togni
Mauro
M
Pusch
Rico
R
Heuer
Katja
K
Wang
Xiaoqian
X
Freund
Christian
C
Kasirer-Friede
Ana
A
Menasche
Gael
G
Koretzky
Gary A
GA
Schraven
Burkhart
B
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
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