ArticleOncogene2003
Protein kinase Calpha activation by RET: evidence for a negative feedback mechanism controlling RET tyrosine kinase.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 31 citations in OpenAlex.
- Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Preclinical Pharmacokinetics and in vitro Metabolism of FHND5071, a Novel Selective RET Kinase Inhibitor.European journal of drug metabolism and pharmacokinetics · 2023Article
- Review
- Personalized Medicine in Medullary Thyroid Carcinoma: A Broad Review of Emerging Treatments.Journal of personalized medicine · 2023Review
- Precision therapy for RET-altered cancers with RET inhibitors.Trends in cancer · 2021Review
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Targeted Therapy For RET-Rearranged Non-Small Cell Lung Cancer: Clinical Development And Future Directions.OncoTargets and therapy · 2019Article
- Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes.Nature reviews. Clinical oncology · 2018Review
- Intracellular signal transduction and modification of the tumor microenvironment induced by RET/PTCs in papillary thyroid carcinoma.Frontiers in endocrinology · 2012Article
- Differential requirement of Tyr1062 multidocking site by RET isoforms to promote neural cell scattering and epithelial cell branching.Oncogene · 2004Article
- A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia.Molecular and cellular biology · 2004Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
We have studied the role of protein kinase C (PKC) in signaling of the RET tyrosine kinase receptor. By using a chimeric receptor (E/R) in which RET kinase can be tightly controlled by the addition of epidermal growth factor (EGF), we have found that RET triggering induces a strong increase of PKCalpha, PKCdelta and PKCzeta activity and that PKCalpha, not PKCdelta and PKCzeta, forms a ligand-dependent protein complex with E/R. We have identified tyrosine 1062 in the RET carboxyl-terminal tail as the docking site for PKCalpha. Block of PKC activity by bisindolylmaleimide or chronic phorbol esters treatment decreased EGF-induced serine/threonine phosphorylation of E/R, while it caused a similarly sized increase of EGF-induced E/R tyrosine kinase activity and mitogenic signaling. Conversely, acute phorbol esters treatment, which promotes PKC activity, increased the levels of E/R serine/threonine phosphorylation and significantly decreased its phosphotyrosine content. A threefold reduction of tyrosine phosphorylation levels of the constitutively active RET/MEN2A oncoprotein was observed upon coexpression with PKCalpha. We conclude that RET binds to and activates PKCalpha. PKCalpha, in turn, causes RET phosphorylation and downregulates RET tyrosine kinase and downstream signaling, thus functioning as a negative feedback loop to modulate RET activity.
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What OpenQuestion holds
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.