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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.
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https://www.hal.inserm.fr/inserm-02440345
Contributor : Gaël Ménasché <>
Submitted on : Wednesday, January 15, 2020 - 10:28:19 AM
Last modification on : Thursday, April 30, 2020 - 3:12:06 PM

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Stefanie Kliche, Dennis Breitling, Mauro Togni, Rico Pusch, Katja Heuer, et al.. The ADAP/SKAP55 Signaling Module Regulates T-Cell Receptor-Mediated Integrin Activation through Plasma Membrane Targeting of Rap1. Molecular and Cellular Biology, American Society for Microbiology, 2006, 26 (19), pp.7130-7144. ⟨10.1128/MCB.00331-06⟩. ⟨inserm-02440345⟩

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