ArticleMolecular and cellular biology2017
Extracellular Signal-Regulated Kinases 1 and 2 Phosphorylate Gab2 To Promote a Negative-Feedback Loop That Attenuates Phosphoinositide 3-Kinase/Akt Signaling.
Article in Molecular and cellular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Infection-Dependent Modulation of the Host Adaptor Gab2 During Chlamydia trachomatis Intracellular Development.Microbiology and immunology · 2026Article
- Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer.NPJ precision oncology · 2024Article
- Epigenetic histone modification by butyrate downregulates KIT and attenuates mast cell function.Journal of cellular and molecular medicine · 2023Article
- Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling.Nature communications · 2022Article
- SFPQ-ABL1 and BCR-ABL1 use different signaling networks to drive B-cell acute lymphoblastic leukemia.Blood advances · 2022Article
- Review
- PTEN Is Required for The Anti-Epileptic Effects of AMPA Receptor Antagonists in Chronic Epileptic Rats.International journal of molecular sciences · 2020Article
- GAB2 inhibits chondrocyte apoptosis through PI3K-AKT signaling in osteoarthritis.International journal of clinical and experimental pathology · 2020Article
- Receptor Tyrosine Kinases in Development: Insights fromInternational journal of molecular sciences · 2019Review
- Article
- Colorectal cancer cells respond differentially to autophagy inhibition in vivo.Scientific reports · 2019Article
- Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRASBritish journal of cancer · 2019Article
- Unique properties of PTEN-L contribute to neuroprotection in response to ischemic-like stress.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The scaffolding adapter protein Gab2 (Grb2-associated binder) promotes cell proliferation, survival, and motility by engaging several signaling pathways downstream of growth factor and cytokine receptors. In particular, Gab2 plays essential roles in mast cells, as it is required for phosphoinositide 3-kinase (PI3K) activation in response to Kit and the high-affinity IgE receptor. While the positive role of Gab2 in PI3K signaling is well documented, very little is known about the mechanisms that attenuate its function. Here we show that Gab2 becomes phosphorylated on multiple proline-directed sites upon stimulation of the Ras/extracellular signal-regulated kinase (ERK) signaling pathway. We demonstrate that ERK1 and ERK2 interact with Gab2 via a novel docking motif, which is required for subsequent Gab2 phosphorylation in response to ERK1/2 activation. We identified four ERK1/2-dependent phosphorylation sites in Gab2 that prevent the recruitment of the p85 regulatory subunit of PI3K. Using bone marrow-derived mast cells to study Gab2-dependent signaling, we found that the inhibition of ERK1/2 activity promotes Akt signaling in response to Kit and the high-affinity IgE receptor. Together, our results indicate that ERK1/2 participates in a negative-feedback loop that attenuates PI3K/Akt signaling in response to various agonists.
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Registered trials
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