ArticleOncogene2006
Phosphorylation of neurofibromin by PKC is a possible molecular switch in EGF receptor signaling in neural cells.
Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 78 citations in OpenAlex.
- Repurposing screens reveal a role for PKCη and NF1 in SARS-CoV-2 infection.PLoS pathogens · 2026Article
- Review
- Genotype-phenotype correlations of neurofibromatosis type 1: a cross-sectional study from a large Chinese cohort.Journal of neurology · 2024Article
- [Gene therapy strategies and prospects for neurofibromatosis type 1].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Article
- PDE4DIP contributes to colorectal cancer growth and chemoresistance through modulation of the NF1/RAS signaling axis.Cell death & disease · 2023Article
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Clinical characteristics and in silico analysis of congenital pseudarthrosis of the tibia combined with neurofibromatosis type 1 caused by a novelFrontiers in genetics · 2022Article
- Review
- The cryo-EM structure of the human neurofibromin dimer reveals the molecular basis for neurofibromatosis type 1.Nature structural & molecular biology · 2021Article
- Mutational spectrum of NF1 gene in 24 unrelated Egyptian families with neurofibromatosis type 1.Molecular genetics & genomic medicine · 2021Article
- Review
- Nuclear Isoforms of Neurofibromin Are Required for Proper Spindle Organization and Chromosome Segregation.Cells · 2020Article
- Review
- Ras-Specific GTPase-Activating Proteins-Structures, Mechanisms, and Interactions.Cold Spring Harbor perspectives in medicine · 2019Review
- Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844-848.American journal of human genetics · 2018Article
- Identification of Mutation Regions onFrontiers in genetics · 2018Article
- Feedback activation of neurofibromin terminates growth factor-induced Ras activation.Cell communication and signaling : CCS · 2016Article
- The NF1 gene revisited - from bench to bedside.Oncotarget · 2014Review
- Down-regulated Six2 by knockdown of neurofibromin results in apoptosis of metanephric mesenchyme cells in vitro.Molecular and cellular biochemistry · 2014Article
- The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy.Circulation research · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Children with neurofibromatosis (NF1) typically develop central nervous system (CNS) abnormalities, including aberrant proliferation of astrocytes and formation of benign astrocytomas. The NF1 gene encodes neurofibromin, a Ras-GAP, highly expressed in developing neural cells; the mechanism of regulation of neurofibromin as a Ras-GAP, remains however unknown. We now show that, in response to EGF, neurofibromin is in vivo phosphorylated on serine residues by PKC-alpha, in human, rat, and avian CNS cells and cell lines. EGF-induced PKC phosphorylation was prominent in the cysteine/serine-rich domain (CSRD) of neurofibromin, which lies in the N-terminus and upstream of the Ras-GAP domain (GRD), and this modification significantly increased the association of neurofibromin with actin in co-immunoprecipitations. In addition, we show that Ras activation in response to EGF was significantly lowered when C62B cells overexpressed a construct encoding both CSRD + GRD. Moreover, when PKC-alpha was downregulated, the Ras-GAP activity of CSRD + GRD was significantly diminished, whereas overexpressed GRD alone acted as a weaker GAP and in a PKC-independent manner. Most importantly, functional Ras inhibition and EGF signaling shifts were established at the single cell level in C6-derived cell lines stably overexpressing CSRD + GRD, when transient co-overexpression of Ras and PKC-depletion prior to stimulation with EGF-induced mitosis. Taken together, these data provide the first evidence of a functional, allosteric regulation of GRD by CSRD, which requires neurofibromin phosphorylation by PKC and association with the actin cytoskeleton. Our data may suggest a novel mechanism for regulating biological responses to EGF and provide a new aspect for the understanding of the aberrant proliferation seen in the CNS of children with NF1.
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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.