ArticleThe Journal of biological chemistry2011
Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 58 citations in OpenAlex.
- Phenotypic transformation of HCC827 cells revealed by evaluation of human platelet lysate as a sustainable fetal bovine serum replacement.Frontiers in cell and developmental biology · 2026Article
- RET overexpression leads to increased brain metastatic competency in luminal breast cancer.Journal of the National Cancer Institute · 2024Article
- CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- REThinking the role of the RET oncogene in breast cancer.Frontiers in oncology · 2024Review
- RET signaling in breast cancer therapeutic resistance and metastasis.Breast cancer research : BCR · 2023Review
- Aberrant RET expression affects normal mammary gland post-lactation transition, enhancing cancer potential.Disease models & mechanisms · 2022Article
- FAK in Cancer: From Mechanisms to Therapeutic Strategies.International journal of molecular sciences · 2022Review
- Functional and clinical characteristics of focal adhesion kinases in cancer progression.Frontiers in cell and developmental biology · 2022Review
- Roles of Enteric Neural Stem Cell Niche and Enteric Nervous System Development in Hirschsprung Disease.International journal of molecular sciences · 2021Review
- Review
- Ret Receptor Has Distinct Alterations and Functions in Breast Cancer.Journal of mammary gland biology and neoplasia · 2020Review
- GPS 5.0: An Update on the Prediction of Kinase-specific Phosphorylation Sites in Proteins.Genomics, proteomics & bioinformatics · 2020Article
- FAK Structure and Regulation by Membrane Interactions and Force in Focal Adhesions.Biomolecules · 2020Review
- RET in breast cancer: pathogenic implications and mechanisms of drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Review
- Review
- Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.The EMBO journal · 2017Article
- The Interconnections between Autophagy and Integrin-Mediated Cell Adhesion.Journal of molecular biology · 2017Review
- RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements.Cell reports · 2016Article
- Autophagy in adhesion and migration.Journal of cell science · 2016Review
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
Abstract
Whether RET is able to directly phosphorylate and activate downstream targets independently of the binding of proteins that contain Src homology 2 or phosphotyrosine binding domains and whether mechanisms in trans by cytoplasmic kinases can modulate RET function and signaling remain largely unexplored. In this study, oligopeptide arrays were used to screen substrates directly phosphorylated by purified recombinant wild-type and oncogenic RET kinase domain in the presence or absence of small molecule inhibitors. The results of the peptide array were validated by enzyme kinetics, in vitro kinase, and cell-based experiments. The identification of focal adhesion kinase (FAK) as a direct substrate for RET kinase revealed (i) a RET-FAK transactivation mechanism consisting of direct phosphorylation of FAK Tyr-576/577 by RET and a reciprocal phosphorylation of RET by FAK, which crucially is able to rescue the kinase-impaired RET K758M mutant and (ii) that FAK binds RET via its FERM domain. Interestingly, this interaction is abolished upon RET phosphorylation, indicating that RET binding to the FERM domain of FAK is a priming step for RET-FAK transactivation. Finally, our data indicate that FAK inhibitors could be used as potential therapeutic agents for patients with multiple endocrine neoplasia type 2 tumors because both, treatment with the FAK kinase inhibitor NVP-TAE226 and FAK down-regulation by siRNA reduced RET phosphorylation and signaling as well as the proliferation and survival of tumor and transfected cell lines expressing oncogenic RET.
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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.