Distinct roles of SKAP55 domains in microcluster stabilization, adhesion via the TCR, and integrin regulation. (A) SKAP55-dependent multimers enable microcluster stabilization and movement, and are required for adhesion via the TCR and via integrins. Microcluster persistence requires interactions capable of joining LAT, Gads, SLP-76, and ADAP into a minimal signaling complex. Constituents of stable microclusters (e.g., ADAP), may interact directly or indirectly with the actin cytoskeleton to promote T cell adhesion and/or microcluster movement. (B) The SKAP55 DM motif couples SLP-76 microclusters to RIAM and talin, enabling the conformational regulation of integrins via their β chains. (C) Models depicting the maturation or termination of the integrin-activating complex in B. Domains are abbreviated as follows: 4HB, four helix bundle; CC, coiled-coil region; FERM, FAK, ezrin, radixin, and moesin domain; PRR, proline-rich region; RA, Ras-association domain; hSH3, helically extended Src-homology 3 domain; TBH, talin-binding helix.