Critical role for an acidic amino acid region in platelet signaling by the hemITAM (hemi-immunoreceptor tyrosine-based activation motif) containing receptor CLEC-2 (C-type lectin receptor-2)

Research output: Contribution to journalArticle

Authors

  • U Sinha
  • A. Pandey
  • J. A. Eble
  • CA O'Callaghan

Colleges, School and Institutes

Abstract

CLEC-2 is a member of new family of C-type lectin receptors characterized by a cytosolic YXXL downstream of three acidic amino acids in a sequence known as a hemITAM (hemi-immunoreceptor tyrosine-based activation motif). Dimerization of two phosphorylated CLEC-2 molecules leads to recruitment of the tyrosine kinase Syk via its tandem SH2 domains and initiation of a downstream signaling cascade. Using Syk-deficient and Zap-70-deficient cell lines we show that hemITAM signaling is restricted to Syk and that the upstream triacidic amino acid sequence is required for signaling. Using surface plasmon resonance and phosphorylation studies, we demonstrate that the triacidic amino acids are required for phosphorylation of the YXXL. These results further emphasize the distinct nature of the proximal events in signaling by hemITAM relative to ITAM receptors.

Details

Original languageEnglish
Pages (from-to)5127-5135
JournalJournal of Biological Chemistry
Volume288
Issue number7
Early online date21 Dec 2012
Publication statusPublished - 15 Feb 2013

Keywords

  • Cell Signaling, Hemostasis, Platelets, Signal Transduction, Protein-tyrosine Kinase (Tyrosine Kinase), CLEC-2, ITAM, Rhodocytin, Syk, HemITAM