Acta Pharmaceutica Sinica B, 2021 The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach.
Wu Yahong, Min Zhao, Hong-Min Liu
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Shp2 knockdown and Noonan/LEOPARD mutant Shp2-induced gastrulation defects. [PDF]
PLoS Genetics, 2007 Shp2 is a cytoplasmic protein-tyrosine phosphatase that is essential for normal development. Activating and inactivating mutations have been identified in humans to cause the related Noonan and LEOPARD syndromes, respectively.
Chris Jopling +2 more
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Strategies to overcome drug resistance using SHP2 inhibitors
Acta Pharmaceutica Sinica B, 2021 Encoded by PTPN11, the SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) is widely recognized as a carcinogenic phosphatase. As a promising anti-cancer drug target, SHP2 regulates many signaling pathways such as RAS-RAF-ERK, PI3K-AKT
Hao Fang, Xuben Hou, Reham M Elhassan
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A hotspot phosphorylation site on SHP2 drives oncoprotein activation and drug resistance [PDF]
Nature CommunicationsSHP2 is a phosphatase and a critical mediator of receptor tyrosine kinase (RTK)-driven RAS/mitogen-activated protein kinase (MAPK) signaling. Despite promising preclinical data, SHP2 inhibitors have shown minimal clinical efficacy, with no defined ...
Prashath Karunaraj +13 more
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SHP2 suppressed the progression of IL-1β induced cartilage damage via modulating BRD4 associated autophagy and pyroptosis signaling pathway [PDF]
Scientific ReportsTo elucidate the protective mechanism of SHP2 in OA by targeting the BRD4/autophagy/apoptosis axis, focusing on its role in alleviating IL-1β-induced cartilage degradation and mitochondrial dysfunction.
Zhenshuan Zhao +3 more
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Inhibiting SHP2 improves ventricular remodeling by restoring AMPK phosphorylation and mitochondrial homeostasis [PDF]
Cell Communication and SignalingBackground Although mitochondrial dysfunction is an established hallmark of ventricular remodeling, the molecular mechanisms governing this process remain incompletely characterized.
Qiao-Juan Shi +12 more
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Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants [PDF]
EMBO ReportsMissense mutations in PTPN11, which encodes the protein tyrosine phosphatase SHP2, are common in several developmental disorders and cancers. While many mutations disrupt auto-inhibition and hyperactivate SHP2, several do not enhance catalytic activity ...
Anne E van Vlimmeren +8 more
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Allosterically activating SHP2 by oleanolic acid inhibits STAT3–Th17 axis for ameliorating colitis
Acta Pharmaceutica Sinica BSrc homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth, differentiation, and survival.
Yi Zou, Wenjie Guo, Jiazhen Zhu
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SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk [PDF]
AntioxidantsSrc homology 2-domain containing protein tyrosine phosphatase 2 (SHP2), encoded by the Ptpn11 gene (Tyrosine-protein phosphatase non-receptor type 11), is a key downstream effector of PD-1/PD-L1 signaling and is likely important, in addition to immune ...
Silvia Fernanda López Moreno +27 more
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Journal of Experimental Medicine, 2023 Allosteric SHP2 inhibitors are a novel class of compounds that target hyperactive Ras/Mitogen Activated Protein Kinase (MAPK) signaling. In this issue of JEM, Wei et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221563) report a genome-wide CRISPR/Cas9 knockout screen that uncovered novel mechanisms of adaptive resistance to pharmacologic ...
Bogdan Popescu, Kevin Shannon
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