Substrate specificity of protein tyrosine phosphatase: Differential behavior of SHP-1 and SHP-2 towards signal regulation protein SIRP?1

2002 ◽  
Vol 84 (4) ◽  
pp. 840-846 ◽  
Author(s):  
Ashwini K. Mishra ◽  
Aihua Zhang ◽  
Tianqi Niu ◽  
Jian Yang ◽  
Xiaoshan Liang ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Differential Behavior ◽  
Signal Regulation

scholarly journals Molecular Determinants of Substrate Recognition in Hematopoietic Protein-tyrosine Phosphatase

2004 ◽  
Vol 279 (50) ◽  
pp. 52150-52159 ◽  
Author(s):  
Zhonghui Huang ◽  
Bo Zhou ◽  
Zhong-Yin Zhang
Keyword(s):  
Substrate Specificity ◽  
Protein Tyrosine Phosphatase ◽  
Cellular Proliferation ◽  
High Efficiency ◽  
Tyrosine Phosphatase ◽  
Substrate Recognition ◽  
Fold Increase ◽  
Phosphoryl Transfer ◽  
Protein Tyrosine ◽  
Hydrolysis Of

The extracellular signal-regulated protein kinase 2 (ERK2) plays a central role in cellular proliferation and differentiation. Full activation of ERK2 requires dual phosphorylation of Thr183and Tyr185in the activation loop. Tyr185dephosphorylation by the hematopoietic protein-tyrosine phosphatase (HePTP) represents an important mechanism for down-regulating ERK2 activity. The bisphosphorylated ERK2 is a highly efficient substrate for HePTP with akcat/Kmof 2.6 × 106m–1s–1. In contrast, thekcatK/mvalues for the HePTP-catalyzed hydrolysis of Tyr(P) peptides are 3 orders of magnitude lower. To gain insight into the molecular basis for HePTP substrate specificity, we analyzed the effects of altering structural features unique to HePTP on the HePTP-catalyzed hydrolysis ofp-nitrophenyl phosphate, Tyr(P) peptides, and its physiological substrate ERK2. Our results suggest that substrate specificity is conferred upon HePTP by both negative and positive selections. To avoid nonspecific tyrosine dephosphorylation, HePTP employs Thr106in the substrate recognition loop as a key negative determinant to restrain its protein-tyrosine phosphatase activity. The extremely high efficiency and fidelity of ERK2 dephosphorylation by HePTP is achieved by a bipartite protein-protein interaction mechanism, in which docking interactions between the kinase interaction motif in HePTP and the common docking site in ERK2 promote the HePTP-catalyzed ERK2 dephosphorylation (∼20-fold increase inkcat/Km) by increasing the local substrate concentration, and second site interactions between the HePTP catalytic site and the ERK2 substrate-binding region enhance catalysis (∼20-fold increase inkcat/Km) by organizing the catalytic residues with respect to Tyr(P)185for optimal phosphoryl transfer.

scholarly journals Probing Protein-tyrosine Phosphatase Substrate Specificity Using a Phosphotyrosine-containing Phage Library

2003 ◽  
Vol 279 (1) ◽  
pp. 311-318 ◽  
Author(s):  
Sébastien Wälchli ◽  
Xavier Espanel ◽  
Axel Harrenga ◽  
Mario Rossi ◽  
Gianni Cesareni ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Phage Library ◽  
Protein Tyrosine ◽  
Phosphatase Substrate

scholarly journals Structural Basis for Substrate Specificity of Protein-tyrosine Phosphatase SHP-1

2000 ◽  
Vol 275 (6) ◽  
pp. 4066-4071 ◽  
Author(s):  
Jian Yang ◽  
Zhiliang Cheng ◽  
Tianqi Niu ◽  
Xiaoshan Liang ◽  
Zhizhuang Joe Zhao ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Structural Basis ◽  
Protein Tyrosine

scholarly journals Determination of the Substrate Specificity of Protein-tyrosine Phosphatase TULA-2 and Identification of Syk as a TULA-2 Substrate

2010 ◽  
Vol 285 (41) ◽  
pp. 31268-31276 ◽  
Author(s):  
Xianwen Chen ◽  
Lige Ren ◽  
Soochong Kim ◽  
Nicholas Carpino ◽  
James L. Daniel ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine

A Microarray Strategy for Mapping the Substrate Specificity of Protein Tyrosine Phosphatase

2007 ◽  
Vol 46 (40) ◽  
pp. 7700-7703 ◽  
Author(s):  
Maja Köhn ◽  
Marta Gutierrez-Rodriguez ◽  
Pascal Jonkheijm ◽  
Stefan Wetzel ◽  
Ron Wacker ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine
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