A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets

Dafydd H. Thomas; Todd M. Getz; Tiffanny N. Newman; Carol A. Dangelmaier; Nick Carpino; Satya P. Kunapuli; Alexander Y. Tsygankov; James L. Daniel

doi:10.1182/blood-2010-02-268136

A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets

Dafydd H. Thomas
, Todd M. Getz
, Tiffanny N. Newman
, Carol A. Dangelmaier
, Nick Carpino
, Satya P. Kunapuli
, Alexander Y. Tsygankov
, James L. Daniel

Microbiology and Immunology

Temple University

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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.

Original language	English
Pages (from-to)	2570-2578
Number of pages	9
Journal	Blood
Volume	116
Issue number	14
DOIs	https://doi.org/10.1182/blood-2010-02-268136
State	Published - Oct 7 2010

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title = "A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets",

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.",

author = "Thomas, \{Dafydd H.\} and Getz, \{Todd M.\} and Newman, \{Tiffanny N.\} and Dangelmaier, \{Carol A.\} and Nick Carpino and Kunapuli, \{Satya P.\} and Tsygankov, \{Alexander Y.\} and Daniel, \{James L.\}",

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doi = "10.1182/blood-2010-02-268136",

language = "English",

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T1 - A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets

AU - Thomas, Dafydd H.

AU - Getz, Todd M.

AU - Newman, Tiffanny N.

AU - Dangelmaier, Carol A.

AU - Carpino, Nick

AU - Kunapuli, Satya P.

AU - Tsygankov, Alexander Y.

AU - Daniel, James L.

PY - 2010/10/7

Y1 - 2010/10/7

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/77957732143

U2 - 10.1182/blood-2010-02-268136

DO - 10.1182/blood-2010-02-268136

M3 - Article

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AN - SCOPUS:77957732143

SN - 0006-4971

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SP - 2570

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JO - Blood

JF - Blood

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ER -

A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets

Abstract

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