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Identification and characterization of two related murine genes, Eat2a and Eat2b, encoding single SH2-domain adapters.

Immunogenetics | Feb 13, 2006

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. Here we report that, unlike in humans, the mouse and rat Eat2 genes are duplicated with an identical genomic organization. The coding regions of the mouse Eat2a and Eat2b genes share 91% identity at the nucleotide level and 84% at the protein level; similarly, segments of introns are highly conserved. Whereas expression of mouse Eat2a mRNA was detected in multiple tissues, Eat2b was only detectable in mouse natural killer cells, CD8+ T cells, and ovaries, suggesting a very restricted tissue expression of the latter. Both the EAT-2A and EAT-2B coimmunoprecipitated with mouse SLAM in transfected cells and augmented tyrosine phosphorylation of the cytoplasmic tail of SLAM. Both EAT-2A and EAT-2B bind to the Src-like kinases Fyn, Hck, Lyn, Lck, and Fgr, as determined by a yeast two-hybrid assay. However, unlike SAP, the EAT-2 proteins bind to their kinase domains and not to the SH3 domain of these kinases. Taken together, the data suggest that both EAT-2A and EAT-2B are adapters that recruit Src kinases to SLAM family receptors using a mechanism that is distinct from that of SAP.

Pubmed ID: 16425036 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Animals | Antigens, CD | Cells, Cultured | Chromosomes, Artificial, Bacterial | Expressed Sequence Tags | Glycoproteins | Immunoglobulins | Mice | Mice, Congenic | Mice, Inbred C57BL | Molecular Sequence Data | Phosphorylation | Protein Binding | Rats | Receptors, Cell Surface | Sequence Homology, Amino Acid | Signal Transduction | Signaling Lymphocytic Activation Molecule Family Member 1 | Transcription Factors | Transfection | src Homology Domains | src-Family Kinases

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI 15066
  • Agency: FIC NIH HHS, Id: R03TW 006472-03

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