ArticleOncogene2001
The tyrosine phosphatase SHP-2 is required for mediating phosphatidylinositol 3-kinase/Akt activation by growth factors.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
66 citing papers in PubMed, 175 citations in OpenAlex.
- SHP2 as a pivotal modulator of the tumor microenvironment in gastrointestinal cancers: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk.Antioxidants (Basel, Switzerland) · 2025Review
- PTPN11 in cartilage development, adult homeostasis, and diseases.Bone research · 2025Review
- Arthropod autophagy molecules facilitate Anaplasma phagocytophilum infection of Ixodes scapularis tick cells.Communications biology · 2025Article
- Phosphopeptide binding to the N-SH2 domain of tyrosine phosphatase SHP2 correlates with the unzipping of its central β-sheet.Computational and structural biotechnology journal · 2024Article
- Integration of transcriptomics, proteomics and loss-of-function screening reveals WEE1 as a target for combination with dasatinib against proneural glioblastoma.Cancer letters · 2024Article
- Folding and Binding Kinetics of the Tandem of SH2 Domains from SHP2.International journal of molecular sciences · 2024Article
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.Cancer discovery · 2023Review
- New Approaches to Targeted Therapy in Melanoma.Cancers · 2023Review
- Discovery of a Novel Series of Imidazopyrazine Derivatives as Potent SHP2 Allosteric Inhibitors.ACS medicinal chemistry letters · 2023Article
- Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with Protein Tyrosine Phosphatase Non-Receptor Type 11 Gene Mutation.Pharmacogenomics and personalized medicine · 2023Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- Current understanding of CTLA-4: from mechanism to autoimmune diseases.Frontiers in immunology · 2023Review
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Fyn and TOM1L1 are recruited to clathrin-coated pits and regulate Akt signaling.The Journal of cell biology · 2022Article
- Targeting SHP2 phosphatase in breast cancer overcomes RTK-mediated resistance to PI3K inhibitors.Breast cancer research : BCR · 2022Article
- Therapeutic Targets of KRAS in Colorectal Cancer.Cancers · 2021Review
- Determining folding and binding properties of the C-terminal SH2 domain of SHP2.Protein science : a publication of the Protein Society · 2021Article
- SHP2 promotes proliferation of breast cancer cells through regulating Cyclin D1 stabilityCancer biology & medicine · 2020Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SHP-2 is a ubiquitously expressed non-transmembrane tyrosine phosphatase with two SH2 domains. Multiple reverse-genetic studies have indicated that SHP-2 is a required component for organ and animal development. SHP-2 wild-type and homozygous mutant mouse fibroblast cells in which the N-terminal SH2 domain was target-deleted were used to examine the function of SHP-2 in regulating Phosphatidylinositol 3-Kinase (PI3K) activation by growth factors. In addition, SHP-2 and various mutants were introduced into human glioblastoma cells as well as SHP-2(-/-) mouse fibroblasts. We found that EGF stimulation and EGFR oncoprotein (DeltaEGFR) expression independently induced the co-immunoprecipitation of the p85 subunit of PI3K with SHP-2. Targeted deletion of the N-terminal SH2 domain of SHP-2 severely impaired PDGF- and IGF-induced Akt phosphorylation. Ectopic expression of SHP-2 in U87MG gliobastoma cells elevated EGF-induced Akt phosphorylation, and the effect was abolished by mutation of its N-terminal SH2 domain. Likewise, the reconstitution of SHP-2 expression in the SHP-2(-/-) cells enhanced Akt phosphorylation induced by EGF while rescuing that induced by PDGF and IGF. Further lipid kinase activity assays confirmed that SHP-2 modulation of Akt phosphorylation correlated with its regulation of PI3K activation. Based on these results, we conclude that SHP-2 is required for mediating PI3K/Akt activation, and the N-terminal SH2 domain is critically important for a "positive" role of SHP-2 in regulating PI3K pathway activation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.