ArticleThe EMBO journal2008
Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein.
Article in The EMBO journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- A tandem recruitment site in the pseudokinase scaffold PEAK3 is subject to phosphorylation-dependent regulation and cancer-associated mutations.The Journal of biological chemistry · 2026Article
- Fragment-Based Interrogation of the 14-3-3/TAZ Protein-Protein Interaction.Biochemistry · 2024Article
- An analysis of the role of GAB2 in pan-cancer from a multidimensional perspective.Discover oncology · 2024Article
- Mast cell deficiency prevents BCR::ABL1 induced splenomegaly and cytokine elevation in a CML mouse model.Leukemia · 2023Article
- Article
- 14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases.Trends in pharmacological sciences · 2021Review
- Dissecting the sequence determinants for dephosphorylation by the catalytic subunits of phosphatases PP1 and PP2A.Nature communications · 2020Article
- Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer.Nature communications · 2019Article
- Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells.Nature medicine · 2018Article
- Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles.Oncotarget · 2016Article
- Changes in Gab2 phosphorylation and interaction partners in response to interleukin (IL)-2 stimulation in T-lymphocytes.Scientific reports · 2016Article
- Microarray Analyses Reveal Marked Differences in Growth Factor and Receptor Expression Between 8-Cell Human Embryos and Pluripotent Stem Cells.Stem cells and development · 2016Article
- Structure and function of Gab2 and its role in cancer (Review).Molecular medicine reports · 2015Review
- SerpinB2 (PAI-2) Modulates Proteostasis via Binding Misfolded Proteins and Promotion of Cytoprotective Inclusion Formation.PloS one · 2015Article
- Receptor tyrosine kinase (RTK) signalling in the control of neural stem and progenitor cell (NSPC) development.Molecular neurobiology · 2014Review
- A (selective) history of Australian involvement in cytokine biology.Cytokine & growth factor reviews · 2013Review
- Article
- Alterations of Gab2 signalling complexes in imatinib and dasatinib treated chronic myeloid leukaemia cells.Cell communication and signaling : CCS · 2013Article
- Gab2 phosphorylation by RSK inhibits Shp2 recruitment and cell motility.Molecular and cellular biology · 2013Article
- Gab2 signaling in chronic myeloid leukemia cells confers resistance to multiple Bcr-Abl inhibitors.Leukemia · 2013Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Grb2-associated binder (Gab)2 functions downstream of a variety of receptor and cytoplasmic tyrosine kinases as a docking platform for specific signal transducers and performs important functions in both normal physiology and oncogenesis. Gab2 signalling is promoted by its association with specific receptors through the adaptor Grb2. However, the molecular mechanisms that attenuate Gab2 signals have remained unclear. We now demonstrate that growth factor-induced phosphorylation of Gab2 on two residues, S210 and T391, leads to recruitment of 14-3-3 proteins. Together, these events mediate negative-feedback regulation, as Gab2(S210A/T391A) exhibits sustained receptor association and signalling and promotes cell proliferation and transformation. Importantly, introduction of constitutive 14-3-3-binding sites into Gab2 renders it refractory to receptor activation, demonstrating that site-selective binding of 14-3-3 proteins is sufficient to terminate Gab2 signalling. Furthermore, this is associated with reduced binding of Grb2. This leads to a model where signal attenuation occurs because 14-3-3 promotes dissociation of Gab2 from Grb2, and thereby uncouples Gab2 from the receptor complex. This represents a novel regulatory mechanism with implications for diverse tyrosine kinase signalling systems.
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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.