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.

Original languageEnglish
Pages (from-to)1440-1445
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Jul 14 2006


  • BTLA
  • Grb-2
  • ITIM
  • PI3K p85
  • Phosphopeptides


Dive into the research topics of 'Association of Grb-2 and PI3K p85 with phosphotyrosile peptides derived from BTLA'. Together they form a unique fingerprint.

Cite this