| First Author | Wang H | Year | 2004 |
| Journal | J Exp Med | Volume | 200 |
| Issue | 8 | Pages | 1063-74 |
| PubMed ID | 15477347 | Mgi Jnum | J:94914 |
| Mgi Id | MGI:3522077 | Doi | 10.1084/jem.20040780 |
| Citation | Wang H, et al. (2004) ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation. J Exp Med 200(8):1063-74 |
| abstractText | T cell-APC conjugation as mediated by leukocyte function-associated antigen-1 (LFA-1)-intercellular adhesion molecule (ICAM)-1 binding is followed by formation of the supramolecular activation cluster (SMAC) at the immunological synapse. The intracellular processes that regulate SMAC formation and its influence on T cell function are important questions to be addressed. Here, using a mutational approach, we demonstrate that binding of adaptor adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76 differentially regulates peripheral SMAC (pSMAC) formation relative to conjugation. Although mutation of the YDDV sites (termed M12) disrupted SLP-76 SH2 domain binding and prevented the ability of ADAP to increase conjugation and LFA-1 clustering, M12 acted selectively as a dominant negative (DN) inhibitor of pSMAC formation, an effect that was paralleled by a DN effect on interleukin-2 production. ADAP also colocalized with LFA-1 at the immunological synapse. Our findings identify ADAP-SLP-76 binding as a signaling event that differentially regulates SMAC formation, and support a role for SMAC formation in T cell cytokine production. |
