Disease relevance of SH2D1B

• Human EAT-2 transcripts were identified by reverse transcriptase-polymerase chain reaction (RT-PCR) in Ewing's sarcoma cell tumour cell lines [1].

High impact information on SH2D1B

• 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 [2].
• Here we report that a second gene encoding a free SH2 domain, EAT-2, is expressed in macrophages and B lympho cytes [2].
• 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 [2].
• Interestingly, overexpression of SAP, but not its homolog EAT-2, leads to a synergistic activation of nuclear factor of activating T cells (NFAT) in combination with a calcium signal in T cells [3].
• The ability of SLAM family receptors to regulate NK cell functions seems to be largely dependent on their capacity to associate, by way of their cytoplasmic domain, with members of the SAP family of adapters, including SAP, Ewing's sarcoma-activated transcript-2 (EAT-2), and EAT-2-related transducer (ERT) [4].

Biological context of SH2D1B

• We show that association of EAT-2 induces the phosphorylation of CRACC and that this process is partially reduced by a pharmacological inhibitor of Src kinases [5].
• We have characterized a novel gene, EWS/FLI1 activated transcript 2 (EAT-2) that was cloned from a murine cDNA library using a differentially expressed RDA fragment [1].
• SAP and EAT-2 define a new class of adaptor proteins composed almost exclusively of a Src homology 2 (SH2) domain [6].

Anatomical context of SH2D1B

• SF2000, which is co-expressed with SAP in T cells, binds both SAP and EAT-2 [7].
• EAT-2, a SAP-related adapter protein, is already detectable in resting NK cells and does not change its expression after IL-2 stimulation [8].
• CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2 [9].
• Two such MAbs, Eat1 and Eat2 (for Extracellular Anti-TAPA1), were used to assess the expression and function of CD81 on murine lymphocytes [10].

Associations of SH2D1B with chemical compounds

• Human EAT-2 (SH2D1B) and SLAM-associated protein (SAP) (SH2D1A) are single SH2-domain adapters, which bind to specific tyrosine residues in the cytoplasmic tail of six signaling lymphocytic activation molecule (SLAM) (SLAMF1)-related receptors [11].

Other interactions of SH2D1B

• Moreover, EAT-2 also associates with 2B4 predominantly in resting NK cells, whereas SAP preferentially binds 2B4 upon activation [5].
• We show that NTB-A is tyrosine phosphorylated in unstimulated human NK cells and associates with SLAM-associated protein (SAP) and EAT-2 [12].

Analytical, diagnostic and therapeutic context of SH2D1B

• CD84 became rapidly phosphorylated on tyrosine residues following ligation with a specific monoclonal antibody and recruited the cytoplasmic adaptor proteins SAP and EAT-2 [9].

References