ArticleMolecular and cellular biology2015
Kinase regulation by hydrophobic spine assembly in cancer.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 138 citations in OpenAlex.
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- Molecular dynamics simulations provide insights into ULK-101 potency and selectivity toward autophagic kinases ULK1/2.Journal of biomolecular structure & dynamics · 2025Article
- Oncogenic non-V600 mutations evade the regulatory machinery of RAF including the Cdc37/Hsp90 chaperone and the 14-3-3 scaffold.Theranostics · 2025Article
- Multiplexed profiling of intracellular protein abundance, activity, interactions and druggability with LABEL-seq.Nature methods · 2024Article
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- Reversible control of kinase signaling through chemical-induced dephosphorylation.Communications biology · 2024Article
- Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling.eLife · 2024Article
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- Functional characterization of two DYRK1B variants causative of AOMS3.Orphanet journal of rare diseases · 2024Article
- Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain.bioRxiv : the preprint server for biology · 2024Article
- Multiplexed, multimodal profiling of the intracellular activity, interactions, and druggability of protein variants using LABEL-seq.bioRxiv : the preprint server for biology · 2024Article
- The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma.Nature communications · 2024Article
- Structural basis and selectivity of sulfatinib binding to FGFR and CSF-1R.Communications chemistry · 2024Article
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
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- BRAFScience advances · 2023Article
- RAS-independent ERK activation by constitutively active KSR3 in non-chordate metazoa.Nature communications · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
A new model of kinase regulation based on the assembly of hydrophobic spines has been proposed. Changes in their positions can explain the mechanism of kinase activation. Here, we examined mutations in human cancer for clues about the regulation of the hydrophobic spines by focusing initially on mutations to Phe. We identified a selected number of Phe mutations in a small group of kinases that included BRAF, ABL1, and the epidermal growth factor receptor. Testing some of these mutations in BRAF, we found that one of the mutations impaired ATP binding and catalytic activity but promoted noncatalytic allosteric functions. Other Phe mutations functioned to promote constitutive catalytic activity. One of these mutations revealed a previously underappreciated hydrophobic surface that functions to position the dynamic regulatory αC-helix. This supports the key role of the C-helix as a signal integration motif for coordinating multiple elements of the kinase to create an active conformation. The importance of the hydrophobic space around the αC-helix was further tested by studying a V600F mutant, which was constitutively active in the absence of the negative charge that is associated with the common V600E mutation. Many hydrophobic mutations strategically localized along the C-helix can thus drive kinase activation.
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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.