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)

Hughes, C. E. ORCID: https://orcid.org/0000-0002-9790-5820, Sinha, U., Pandey, A., Eble, J. A., O'Callaghan, C. A. and Watson, S. P. (2013) 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). The Journal of Biological Chemistry, 288 (7). pp. 5127-5135. ISSN 1083-351X doi: 10.1074/jbc.M112.411462

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/44572
Identification Number/DOI	10.1074/jbc.M112.411462
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	American Society for Biochemistry and Molecular Biology
Download/View statistics	View download statistics for this item