scholarly journals Counteracting Effects Operating on Src Homology 2 Domain-containing Protein-tyrosine Phosphatase 2 (SHP2) Function Drive Selection of the Recurrent Y62D and Y63C Substitutions in Noonan Syndrome

2012 ◽  
Vol 287 (32) ◽  
pp. 27066-27077 ◽  
Author(s):  
Simone Martinelli ◽  
Aurelio P. Nardozza ◽  
Silvia Delle Vigne ◽  
Gilda Sabetta ◽  
Paola Torreri ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Noonan Syndrome ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain ◽  
Selection Of

scholarly journals Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds

2008 ◽  
Vol 51 (16) ◽  
pp. 4948-4956 ◽  
Author(s):  
Harshani R. Lawrence ◽  
Roberta Pireddu ◽  
Liwei Chen ◽  
Yunting Luo ◽  
Shen-Shu Sung ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain

scholarly journals Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Promotes Inflammation and Accelerates Osteoarthritis by Activating β-Catenin

2021 ◽  
Vol 9 ◽  
Author(s):  
Tenghui Tao ◽  
Danni Luo ◽  
Chenghao Gao ◽  
Hui Liu ◽  
Zehua Lei ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cartilage Degradation ◽  
Mitogen Activated Protein Kinase ◽  
Osteophyte Formation ◽  
Protein Tyrosine ◽  
Src Homology 2 ◽  
Primary Mouse ◽  
Src Homology ◽  
Src Homology 2 Domain

Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation, subchondral bone remodeling and osteophyte formation. Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) has not been fully investigated in the pathogenesis of OA. In this study, we found that SHP2 expression was significantly increased after interleukin-1β (IL-1β) treatment in primary mouse chondrocytes. Inhibition of SHP2 using siRNA reduced MMP3, MMP13 levels, but increased AGGRECAN, COL2A1, SOX9 expression in vitro. On the contrary, overexpression of SHP2 exerted the opposite results and promoted cartilage degradation. Mechanistically, SHP2 activated Wnt/β-catenin signaling possibly through directly binding to β-catenin. SHP2 also induced inflammation through activating Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways. Our in vivo studies showed that SHP2 knockdown effectively delayed cartilage destruction and reduced osteophyte formation in the mouse model of OA induced by destabilization of the medial meniscus (DMM). Altogether, our study identifies that SHP2 is a novel and potential therapeutic target of OA.

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