ArticleMolecular and cellular biology1994
A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase.
Article in Molecular and cellular biology, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed, 463 citations in OpenAlex.
- Posttranslational modifications remodel proteome-wide ligandability.Nature chemical biology · 2026Article
- The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading.Molecular cancer therapeutics · 2024Article
- Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways.The Journal of biological chemistry · 2024Article
- Complex Roles ofAnnual review of cancer biology · 2024Article
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy.Cancer discovery · 2023Article
- KRAS-Dependency in Pancreatic Ductal Adenocarcinoma: Mechanisms of Escaping in Resistance to KRAS Inhibitors and Perspectives of Therapy.International journal of molecular sciences · 2023Review
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- Cell cycle control by the insulin-like growth factor signal: at the crossroad between cell growth and mitotic regulation.Cell cycle (Georgetown, Tex.) · 2023Review
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2.Frontiers in cell and developmental biology · 2022Review
- Strategies to overcome drug resistance using SHP2 inhibitors.Acta pharmaceutica Sinica. B · 2021Review
- Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer.Molecular cancer · 2021Review
- The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors.Nature communications · 2021Article
- Targeting KRAS in pancreatic cancer: new drugs on the horizon.Cancer metastasis reviews · 2021Review
- A structural perspective on targeting the RTK/Ras/MAP kinase pathway in cancer.Protein science : a publication of the Protein Society · 2021Review
- Phosphotyrosine couples peptide binding and SHP2 activation via a dynamic allosteric network.Computational and structural biotechnology journal · 2021Article
- RAS-targeted therapies: is the undruggable drugged?Nature reviews. Drug discovery · 2020Review
- Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation.Nature communications · 2019Article
- SHP-2 in Lymphocytes' Cytokine and Inhibitory Receptor Signaling.Frontiers in immunology · 2019Review
77 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Autophosphorylated growth factor receptors provide binding sites for the src homology 2 domains of intracellular signaling molecules. In response to epidermal growth factor (EGF), the activated EGF receptor binds to a complex containing the signaling protein GRB2 and the Ras guanine nucleotide-releasing factor Sos, leading to activation of the Ras signaling pathway. We have investigated whether the platelet-derived growth factor (PDGF) receptor binds GRB2-Sos. In contrast with the EGF receptor, the GRB2 does not bind to the PDGF receptor directly. Instead, PDGF stimulation induces the formation of a complex containing GRB2; 70-, 80-, and 110-kDa tyrosine-phosphorylated proteins; and the PDGF receptor. Moreover, GRB2 binds directly to the 70-kDa protein but not to the PDGF receptor. Using a panel of PDGF beta-receptor mutants with altered tyrosine phosphorylation sites, we identified Tyr-1009 in the PDGF receptor as required for GRB2 binding. Binding is inhibited by a phosphopeptide containing a YXNX motif. The protein tyrosine phosphatase Syp/PTP1D/SHPTP2/PTP2C is approximately 70 kDa, binds to the PDGF receptor via Tyr-1009, and contains several YXNX sequences. We found that the 70-kDa protein that binds to the PDGF receptor and to GRB2 comigrates with Syp and is recognized by anti-Syp antibodies. Furthermore, both GRB2 and Sos coimmunoprecipitate with Syp from lysates of PDGF-stimulated cells, and GRB2 binds directly to tyrosine-phosphorylated Syp in vitro. These results indicate that GRB2 interacts with different growth factor receptors by different mechanisms and the cytoplasmic phosphotyrosine phosphatase Syp acts as an adapter between the PDGF receptor and the GRB2-Sos complex.
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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.