ArticleProceedings of the National Academy of Sciences of the United States of America2008
CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- The CNK-HYP scaffolding complex promotes RAF activation by enhancing KSR-MEK interaction.Nature structural & molecular biology · 2024Article
- Structural analysis of the SAM domain of the Arabidopsis mitochondrial tRNA import receptor.The Journal of biological chemistry · 2024Article
- CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling.Nature communications · 2023Article
- Review
- The Evolutionary Kaleidoscope of Rhodopsins.mSystems · 2022Article
- Diacylglycerol kinase δ and sphingomyelin synthase-related protein functionally interact via their sterile α motif domains.The Journal of biological chemistry · 2020Article
- Structure of the SLy1 SAM homodimer reveals a new interface for SAM domain self-association.Scientific reports · 2019Article
- Regulatory mechanisms of EGFR signalling during Drosophila eye development.Cellular and molecular life sciences : CMLS · 2016Review
- Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3.BMC structural biology · 2014Article
- The CNK2 scaffold interacts with vilse and modulates Rac cycling during spine morphogenesis in hippocampal neurons.Current biology : CB · 2014Article
- Heterotypic Sam-Sam association between Odin-Sam1 and Arap3-Sam: binding affinity and structural insights.Chembiochem : a European journal of chemical biology · 2013Article
- A CC-SAM, for coiled coil-sterile α motif, domain targets the scaffold KSR-1 to specific sites in the plasma membrane.Science signaling · 2012Article
- Solution structure of the first Sam domain of Odin and binding studies with the EphA2 receptor.Biochemistry · 2012Article
- NMR structure of a heterodimeric SAM:SAM complex: characterization and manipulation of EphA2 binding reveal new cellular functions of SHIP2.Structure (London, England : 1993) · 2012Article
- Loss-of-Function CNKSR2 Mutation Is a Likely Cause of Non-Syndromic X-Linked Intellectual Disability.Molecular syndromology · 2012Article
- A human sterile alpha motif domain polymerizome.Protein science : a publication of the Protein Society · 2011Article
- Mechanistic principles of RAF kinase signaling.Cellular and molecular life sciences : CMLS · 2011Review
- The CNK1 scaffold binds cytohesins and promotes insulin pathway signaling.Genes & development · 2010Article
- Drosophila Raf's N terminus contains a novel conserved region and can contribute to torso RTK signaling.Genetics · 2010Article
- The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact with Arap3-Sam and EphA2-Sam.BMC structural biology · 2009Article
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RAF kinase functions in the mitogen-activated protein kinase (MAPK) pathway to transmit growth signals to the downstream kinases MEK and ERK. Activation of RAF catalytic activity is facilitated by a regulatory complex comprising the proteins CNK (Connector enhancer of KSR), HYP (Hyphen), and KSR (Kinase Suppressor of Ras). The sterile alpha-motif (SAM) domain found in both CNK and HYP plays an essential role in complex formation. Here, we have determined the x-ray crystal structure of the SAM domain of CNK in complex with the SAM domain of HYP. The structure reveals a single-junction SAM domain dimer of 1:1 stoichiometry in which the binding mode is a variation of polymeric SAM domain interactions. Through in vitro and in vivo mutational analyses, we show that the specific mode of dimerization revealed by the crystal structure is essential for RAF signaling and facilitates the recruitment of KSR to form the CNK/HYP/KSR regulatory complex. We present two docking-site models to account for how SAM domain dimerization might influence the formation of a higher-order CNK/HYP/KSR complex.
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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.