ArticleProceedings of the National Academy of Sciences of the United States of America2001
Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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Who cites it
138 citing papers in PubMed, 312 citations in OpenAlex.
- Anastrozole and everolimus in advanced gynecologic and breast malignancies: activity and molecular alterations in the PI3K/AKT/mTOR pathway.Oncotarget · 2014Trial
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- The Caenorhabditis elegans protein SOC-3 permits an alternative mode of signal transduction by the EGL-15 FGF receptor.Developmental biology · 2024Article
- Article
- Hsa_circ_0007765 Promotes Platelet-Derived Growth Factor-BB-Induced Proliferation and Migration of Human Aortic Vascular Smooth Muscle Cells in Atherosclerosis.Cardiovascular toxicology · 2024Article
- Fibroblast growth factor receptor signaling in estrogen receptor-positive breast cancer: mechanisms and role in endocrine resistance.Frontiers in oncology · 2024Review
- Fibroblast growth factor signaling in axons: from development to disease.Cell communication and signaling : CCS · 2023Review
- The Role of GAB1 in Cancer.Cancers · 2023Review
- Review
- Review
- Metabolic Messengers: fibroblast growth factor 1.Nature metabolism · 2022Review
- Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects.Blood cancer journal · 2022Article
- Prognostic Characteristics of Immune-Related Genes and the Related Regulatory Axis in Patients With Stage N+M0 Breast Cancer.Frontiers in oncology · 2022Article
- Review
- Translational control in neurovascular brain development.Royal Society open science · 2021Review
- Review
- Lacrimal gland budding requires PI3K-dependent suppression of EGF signaling.Science advances · 2021Article
- Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling.Cells · 2021Review
- FGF/FGFR Signaling in Hepatocellular Carcinoma: From Carcinogenesis to Recent Therapeutic Intervention.Cancers · 2021Review
- Targeting Aberrant FGFR Signaling to Overcome CDK4/6 Inhibitor Resistance in Breast Cancer.Cells · 2021Review
78 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The docking protein FRS2 is a major downstream effector that links fibroblast growth factor (FGF) and nerve growth factor receptors with the Ras/mitogen-activated protein kinase signaling cascade. In this report, we demonstrate that FRS2 also plays a pivotal role in FGF-induced recruitment and activation of phosphatidylinositol 3-kinase (PI3-kinase). We demonstrate that tyrosine phosphorylation of FRS2alpha leads to Grb2-mediated complex formation with the docking protein Gab1 and its tyrosine phosphorylation, resulting in the recruitment and activation of PI3-kinase. Furthermore, Grb2 bound to tyrosine-phosphorylated FRS2 through its SH2 domain interacts primarily via its carboxyl-terminal SH3 domain with a proline-rich region in Gab1 and via its amino-terminal SH3 domain with the nucleotide exchange factor Sos1. Assembly of FRS2alpha:Grb2:Gab1 complex induced by FGF stimulation results in activation of PI3-kinase and downstream effector proteins such as the S/T kinase Akt, whose cellular localization and activity are regulated by products of PI3-kinase. These experiments reveal a unique mechanism for generation of signal diversity by growth factor-induced coordinated assembly of a multidocking protein complex that can activate the Ras/mitogen-activated protein kinase cascade to induce cell proliferation and differentiation, and PI3-kinase to activate a mediator of a cell survival pathway.
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