title: T cell activation is reduced by the catalytically inactive form of protein tyrosine phosphatase SHP-2.
abstract: Src-homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is a ubiquitously expressed cytosolic tyrosine phosphatase implicated in many different signaling pathways involving cytokine receptors and T and B cell receptors; however, the precise functional role of SHP-2 in T cell signaling is not entirely clear. In this study, we overexpressed a catalytically inactive form of SHP-2 with a classic cysteine 459-to-serine mutation (dnSHP-2) to elucidate the in vivo effects of SHP-2 on T cells. We found that mice overexpressing dnSHP-2 showed reduced T cell activation, presumably due to increased tyrosine phosphorylation of Grb2-binding protein (Gab2) and inhibition of mitogen-activated protein kinase (MAPK) activity. SHP-2 appears to be a positive regulator of the MAPK pathway in T cells, likely through coupling of the multimeric complex to the Ras/MAPK pathway. However, SHP-2 does not appear to affect T cell antigen receptor (TCR)-evoked calcium mobilization, stress-activated protein kinase/c-jun N-terminal kinases (SAPK/JNKs) activation, or overall tyrosine phosphorylation.
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University Xi'an, Shanxi Province, China.
authors.forename: Baoxia
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University Guangzhou, Guangdong, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University Xi'an, Shanxi Province, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University Xi'an, Shanxi Province, China.
authors.forename: Guangxun
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University Xi'an, Shanxi Province, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Hematology, Xijing Hospital, Fourth Military Medical University Xi'an, Shanxi Province, China.
authors.forename: Xiequn
authors.initials: X
authors.lastname: Chen
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital Ontario, Canada.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Zhang
keywords: Gab2; Ras/MAPK pathway; Src-homology 2 domain-containing tyrosine phosphatase-2; T cell; transgenic mice