EAT-2 Functions Like SAP

Abstract

The signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) is expressed in T lymphocytes and natural killer (NK) cells. SAP, which consists of only slightly more than an Src homology 2 (SH2) domain, is critical to proper signaling by SLAM; mutations in SAP that prevent its binding to SLAM lead to X-linked lymphoproliferative disease. Now, a similar protein, termed EAT-2, expressed in B lymphocytes and macrophages, has been implicated in the signaling pathways of the antigen-presenting cell receptors CD84, CD229, CD244, and SLAM. EAT-2 bound to the tyrosine phosphorylated forms of the aforementioned receptors, but in contrast to SAP, EAT-2 did not bind unphosphorylated SLAM. The structure of EAT-2 in complex with a phosphorylated peptide highly resembled the structure of SLAM with a similar peptide. As is the case with SLAM, EAT-2 inhibited the recruitment of the protein tyrosine phosphatase SHP-2 to the receptors. Thus, the data indicate that EAT-2 and SAP are members of a protein family with similar structure and function, but whose expression appears exclusive. M. Morra, J. Lu, F. Poy, M. Martin, J. Sayos, S. Calpe, C. Gullo, D. Howie, S. Rietdijk, A. Thompson, A. J. Coyle, C. Denny, M. B. Yaffe, P. Engel, M. J. Eck, C. Terhorst, Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells. EMBO J. 20 , 5840-5852 (2001). [Abstract] [Full Text]