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A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2.
- Source :
-
Blood [Blood] 2006 Jan 15; Vol. 107 (2), pp. 542-9. Date of Electronic Publication: 2005 Sep 20. - Publication Year :
- 2006
-
Abstract
- The snake venom rhodocytin has been reported to bind to integrin alpha2beta1 and glycoprotein (GP) Ibalpha on platelets, but it is also able to induce activation independent of the 2 receptors and of GPVI. Using rhodocytin affinity chromatography, we have identified a novel C-type lectin receptor, CLEC-2, in platelets that confers signaling responses to rhodocytin when expressed in a cell line. CLEC-2 has a single tyrosine residue in a YXXL motif in its cytosolic tail, which undergoes tyrosine phosphorylation upon platelet activation by rhodocytin or an antibody to CLEC-2, but not to collagen, thrombin receptor agonist peptide (TRAP), or convulxin. Tyrosine phosphorylation of CLEC-2 and other signaling proteins by rhodocytin is inhibited by the Src family kinase inhibitor PP2. Further, activation of murine platelets by rhodocytin is abolished in the absence of Syk and PLCgamma2, and partially reduced in the absence of LAT, SLP-76, and Vav1/Vav3. These findings define a novel signaling pathway in platelets whereby activation of CLEC-2 by rhodocytin leads to tyrosine phosphorylation of its cytosolic tail, binding of Syk and initiation of downstream tyrosine phosphorylation events, and activation of PLCgamma2. CLEC-2 is the first C-type lectin receptor to be found on platelets which signals through this novel pathway.
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Signal Transducing physiology
Animals
Antibodies, Monoclonal immunology
Blotting, Western
Collagen metabolism
Crotalid Venoms pharmacology
Cytosol metabolism
Enzyme Precursors genetics
Flow Cytometry
Guanine Nucleotide Exchange Factors genetics
Guanine Nucleotide Exchange Factors physiology
Humans
Immunoprecipitation
Intracellular Signaling Peptides and Proteins
Lectins, C-Type immunology
Membrane Proteins genetics
Membrane Proteins physiology
Mice
Mice, Knockout
Peptide Fragments
Phospholipase C gamma genetics
Phospholipase C gamma physiology
Phosphoproteins genetics
Phosphoproteins physiology
Phosphorylation
Platelet Aggregation
Protein-Tyrosine Kinases genetics
Proto-Oncogene Proteins c-vav genetics
Proto-Oncogene Proteins c-vav physiology
Pyrimidines pharmacology
Receptors, Gastrointestinal Hormone
Receptors, Immunologic immunology
Receptors, Neuropeptide Y
Receptors, Thrombin
Syk Kinase
Tyrosine metabolism
Enzyme Precursors metabolism
Lectins, C-Type metabolism
Platelet Activation
Protein-Tyrosine Kinases metabolism
Receptors, Immunologic metabolism
Signal Transduction
Viper Venoms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 107
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 16174766
- Full Text :
- https://doi.org/10.1182/blood-2005-05-1994