Association of Grb-2 and PI3K p85 with phosphotyrosile peptides derived from BTLA.

B and T lymphocyte attenuator (BTLA) is a recently identified inhibitory receptor expressed by B and T cells. We previously identified two tyrosine-containing signaling motifs in the cytoplasmic domain of BTLA that interact with the SHP-1 and SHP-2 phosphatases. BTLA has a third conserved tyrosine-containing motif within the cytoplasmic domain, ...
similar in sequence to a Grb-2 recruitment site. To identify specific interacting proteins that would be recruited to this motif, we carried out an unbiased screen by using synthetic peptides in active (e.g., phosphotyrosil-containing) or control (e.g., non-phosphorylated) forms as baits. Using mass spectrometry, we identified two specific interacting proteins, Grb-2 and the p85 subunit of PI3K. Further, we demonstrate that the interaction with Grb-2 is direct, whereas the recruitment of the p85 subunit by BTLA phosphotyrosile-containing peptides may be indirect via its association with Grb-2. These findings may provide biochemical basis for previously unexplained actions of BTLA.
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, Blotting, Western, Cell Line, Tumor, GRB2 Adaptor Protein, Glutathione Transferase, Humans, Immunoprecipitation, Mice, Molecular Sequence Data, Oligopeptides, Phosphatidylinositol 3-Kinases, Phosphorylation, Phosphotyrosine, Protein Binding, Protein Subunits, Receptors, Immunologic, Recombinant Fusion Proteins, Sequence Homology, Amino Acid
Biochem. Biophys. Res. Commun.
Date: Jul. 14, 2006
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