ArticleCommunications biology2021
Grb2 binding induces phosphorylation-independent activation of Shp2.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Microglial GRB2 is essential for brain ventriculogenesis and cerebrospinal fluid homeostasis.The Journal of clinical investigation · 2026Article
- SHP-2 Expression Is a Positive Prognostic Biomarker in Non-Small-Cell Lung Carcinoma: Association with KRAS Mutation and Prolonged Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- SHP2 negatively regulates TGF-β signaling by destabilizing the TGF-β type I receptor.Cell communication and signaling : CCS · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Regulation and activity of the phosphatase SHP2: SH2 domains, dephosphorylation activity, and beyond.Biochemical Society transactions · 2026Review
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Synthetic Lethality of SHP2 and XIAP Suppresses Proliferation and Metastasis in KRAS-mutant Nonsmall Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction.Protein science : a publication of the Protein Society · 2025Article
- 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
- Folding and Binding Kinetics of the Tandem of SH2 Domains from SHP2.International journal of molecular sciences · 2024Article
- Assessing TGF-β Prognostic Model Predictions for Chemotherapy Response and Oncogenic Role of FKBP1A in Liver Cancer.Current pharmaceutical design · 2024Article
- SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.Cellular and molecular life sciences : CMLS · 2023Article
- Regulation of microRNA expression by the adaptor protein GRB2.Scientific reports · 2023Article
- Anti-c-MET Fab-Grb2-Gab1 Fusion Protein-Mediated Interference of c-MET Signaling Pathway Induces Methuosis in Tumor Cells.International journal of molecular sciences · 2022Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- The relative binding position of Nck and Grb2 adaptors impacts actin-based motility of Vaccinia virus.eLife · 2022Article
- The structural basis of BCR-ABL recruitment of GRB2 in chronic myelogenous leukemia.Biophysical journal · 2022Article
- TGF-β1/SH2B3 axis regulates anoikis resistance and EMT of lung cancer cells by modulating JAK2/STAT3 and SHP2/Grb2 signaling pathways.Cell death & disease · 2022Article
- T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
The regulation of phosphatase activity is fundamental to the control of intracellular signalling and in particular the tyrosine kinase-mediated mitogen-activated protein kinase (MAPK) pathway. Shp2 is a ubiquitously expressed protein tyrosine phosphatase and its kinase-induced hyperactivity is associated with many cancer types. In non-stimulated cells we find that binding of the adaptor protein Grb2, in its monomeric state, initiates Shp2 activity independent of phosphatase phosphorylation. Grb2 forms a bidentate interaction with both the N-terminal SH2 and the catalytic domains of Shp2, releasing the phosphatase from its auto-inhibited conformation. Grb2 typically exists as a dimer in the cytoplasm. However, its monomeric state prevails under basal conditions when it is expressed at low concentration, or when it is constitutively phosphorylated on a specific tyrosine residue (Y160). Thus, Grb2 can activate Shp2 and downstream signal transduction, in the absence of extracellular growth factor stimulation or kinase-activating mutations, in response to defined cellular conditions. Therefore, direct binding of Grb2 activates Shp2 phosphatase in the absence of receptor tyrosine kinase up-regulation.
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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.