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- Title
Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells.
- Authors
Morra, M; Lu, J; Poy, F; Martin, M; Sayos, J; Calpe, S; Gullo, C; Howie, D; Rietdijk, S; Thompson, A; Coyle, A J; Denny, C; Yaffe, M B; Engel, P; Eck, M J; Terhorst, C
- Abstract
The T and natural killer (NK) cell-specific gene SAP (SH2D1A) encodes a 'free SH2 domain' that binds a specific tyrosine motif in the cytoplasmic tail of SLAM (CD150) and related cell surface proteins. Mutations in SH2D1A cause the X-linked lymphoproliferative disease, a primary immunodeficiency. Here we report that a second gene encoding a free SH2 domain, EAT-2, is expressed in macrophages and B lympho cytes. The EAT-2 structure in complex with a phosphotyrosine peptide containing a sequence motif with Tyr281 of the cytoplasmic tail of CD150 is very similar to the structure of SH2D1A complexed with the same peptide. This explains the high affinity of EAT-2 for the pTyr motif in the cytoplasmic tail of CD150 but, unlike SH2D1A, EAT-2 does not bind to non-phosphorylated CD150. EAT-2 binds to the phosphorylated receptors CD84, CD150, CD229 and CD244, and acts as a natural inhibitor, which interferes with the recruitment of the tyrosine phosphatase SHP-2. We conclude that EAT-2 plays a role in controlling signal transduction through at least four receptors expressed on the surface of professional antigen-presenting cells.
- Publication
The EMBO journal, 2001, Vol 20, Issue 21, p5840
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/20.21.5840