ArticleGenes & development2010
The CNK1 scaffold binds cytohesins and promotes insulin pathway signaling.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 72 citations in OpenAlex.
- Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway.iScience · 2025Article
- ARF: the most misunderstood GTPase I ever knew - why study ARF GAPs.Frontiers in molecular biosciences · 2025Review
- CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling.Nature communications · 2023Article
- Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling.Molecular cancer research : MCR · 2023Article
- ARNO is recruited by the neuronal adaptor FE65 to potentiate ARF6-mediated neurite outgrowth.Open biology · 2022Article
- Physiological and Pathological Roles of the Cytohesin Family in Neurons.International journal of molecular sciences · 2022Review
- Disease-associated synaptic scaffold protein CNK2 modulates PSD size and influences localisation of the regulatory kinase TNIK.Scientific reports · 2020Article
- Arf-GEF localization and function at myosin-rich adherens junctions via coiled-coil heterodimerization with an adaptor protein.Molecular biology of the cell · 2019Article
- An Inhibitor of the Pleckstrin Homology Domain of CNK1 Selectively Blocks the Growth of Mutant KRAS Cells and Tumors.Cancer research · 2019Article
- Inhibition of the IGF-1-PI3K-Akt-mTORC2 pathway in lipid rafts increases neuronal vulnerability in a genetic lysosomal glycosphingolipidosis.Disease models & mechanisms · 2019Article
- ARF GTPases and their GEFs and GAPs: concepts and challenges.Molecular biology of the cell · 2019Review
- Cytohesin-3 is required for full insulin receptor signaling and controls body weight via lipid excretion.Scientific reports · 2019Article
- Cytohesin-2 Is Upregulated in Malignant Melanoma and Contributes to Tumor Growth.Annals of dermatology · 2019Article
- MARK3-mediated phosphorylation of ARHGEF2 couples microtubules to the actin cytoskeleton to establish cell polarity.Science signaling · 2017Article
- Membrane localization of acetylated CNK1 mediates a positive feedback on RAF/ERK signaling.Science advances · 2017Article
- Absence of IQGAP1 Protein Leads to Insulin Resistance.The Journal of biological chemistry · 2017Article
- Optogenetic clustering of CNK1 reveals mechanistic insights in RAF and AKT signalling controlling cell fate decisions.Scientific reports · 2016Article
- S6 Kinase Reflects and Regulates Ethanol-Induced Sedation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Kinome Screen Identifies PFKFB3 and Glucose Metabolism as Important Regulators of the Insulin/Insulin-like Growth Factor (IGF)-1 Signaling Pathway.The Journal of biological chemistry · 2015Article
- The effect of a preparation of minerals, vitamins and trace elements on the cardiac gene expression pattern in male diabetic rats.Cardiovascular diabetology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Protein scaffolds play an important role in signal transduction, regulating the localization of signaling components and mediating key protein interactions. Here, we report that the major binding partners of the Connector Enhancer of KSR 1 (CNK1) scaffold are members of the cytohesin family of Arf guanine nucleotide exchange factors, and that the CNK1/cytohesin interaction is critical for activation of the PI3K/AKT cascade downstream from insulin and insulin-like growth factor 1 (IGF-1) receptors. We identified a domain located in the C-terminal region of CNK1 that interacts constitutively with the coiled-coil domain of the cytohesins, and found that CNK1 facilitates the membrane recruitment of cytohesin-2 following insulin stimulation. Moreover, through protein depletion and rescue experiments, we found that the CNK1/cytohesin interaction promotes signaling from plasma membrane-bound Arf GTPases to the phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) to generate a PIP(2)-rich microenvironment that is critical for the membrane recruitment of insulin receptor substrate 1 (IRS1) and signal transmission to the PI3K/AKT cascade. These findings identify CNK1 as a new positive regulator of insulin signaling.
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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.