Abstract
T-cell ubiquitin ligand-2 (TULA-2) is a recently discovered histidine tyrosine phosphatase thought to be ubiquitously expressed. In this work, we have investigated whether TULA-2 has a key role in platelet glycoprotein VI (GPVI) signaling. This study indicates that TULA-2 is expressed in human and murine platelets and is able to associate with Syk and dephosphorylate it. Ablation of TULA-2 resulted in hyperphosphorylation of Syk and its downstream effector phospholipase C-γ2 as well as enhanced GPVI-mediated platelet functional responses. In addition, shorter bleeding times and a prothrombotic phenotype were observed in mice lacking TULA-2. We therefore propose that TULA-2 is the primary tyrosine phosphatase mediating the dephosphorylation of Syk and thus functions as a negative regulator of GPVI signaling in platelets.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Bleeding Time
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Blood Platelets / metabolism*
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Calcium / metabolism
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Gene Expression
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Gene Knockout Techniques
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mice
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Phospholipase C gamma / metabolism
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Phosphorylation
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Platelet Membrane Glycoproteins / metabolism*
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Protein-Tyrosine Kinases / metabolism*
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Signal Transduction
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Syk Kinase
Substances
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Intracellular Signaling Peptides and Proteins
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Platelet Membrane Glycoproteins
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platelet membrane glycoprotein VI
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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Syk protein, mouse
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Protein Tyrosine Phosphatases
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TULA-2 protein, mouse
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UBASH3B protein, human
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Phospholipase C gamma
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Calcium