Affinage

KSR1

Kinase suppressor of Ras 1 · UniProt Q8IVT5

Length
923 aa
Mass
102.2 kDa
Annotated
2026-04-28
100 papers in source corpus 59 papers cited in narrative 57 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KSR1 is a conserved pseudokinase/scaffold protein that organizes the RAS-RAF-MEK-ERK signaling cascade by constitutively binding MEK and, upon growth factor stimulation, translocating to the plasma membrane to assemble RAF-MEK-ERK complexes and regulate the intensity and duration of ERK activation (PMID:11940661, PMID:15121859, PMID:9427629). Membrane recruitment is controlled by a phosphorylation–dephosphorylation switch: C-TAK1/MARK2-mediated phosphorylation of Ser392 creates a 14-3-3 binding site that sequesters KSR1 in the cytoplasm, while PP2A (recruited via the adaptor GEF-H1) dephosphorylates this site to license membrane translocation, with the CC-SAM domain and atypical C1 domain providing direct membrane-targeting determinants (PMID:11741534, PMID:12932319, PMID:24525234, PMID:23250398). Crystal structures reveal that KSR1 allosterically activates BRAF through side-to-side heterodimerization—driven by CC-SAM/BRS contacts and kinase-domain dimer interfaces—positioning KSR1-bound MEK for phosphorylation by a catalytic RAF protomer, while KSR1 itself retains intrinsic serine kinase activity capable of phosphorylating MEK1 (PMID:21441910, PMID:29433126, PMID:21144847). Beyond canonical MAPK signaling, KSR1 functions in T-cell and NK-cell activation at the immunological synapse, coordinates adipogenic and metabolic transcriptional programs, and its scaffolding is terminated by caspase cleavage during apoptosis and by praja2-mediated ubiquitin-dependent degradation (PMID:19188442, PMID:16107706, PMID:17613518, PMID:27195677).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Genetic screens in Drosophila and C. elegans independently identified KSR as a novel kinase-family gene required for RAS-mediated signal transduction, establishing that a previously unknown component acts between or in parallel to RAS and RAF.

    Evidence Forward genetic suppressor/enhancer screens with epistasis analysis in Drosophila and C. elegans vulval induction

    PMID:8521512 PMID:8521513 PMID:8521514

    Open questions at the time
    • Biochemical activity (kinase vs. scaffold) unknown
    • Mammalian function not yet tested
    • Direct binding partners not identified
  2. 1997 High

    Domain dissection revealed that KSR1 stimulates RAF-1 activity in a kinase-independent manner through its CA3/C1 cysteine-rich domain and translocates from cytoplasm to plasma membrane upon RAS activation, shifting the model from simple kinase to potential scaffold/allosteric activator.

    Evidence Domain mutagenesis, in vitro kinase assays, subcellular fractionation, and Xenopus oocyte maturation assays

    PMID:8946910 PMID:9371754

    Open questions at the time
    • Nature of the 'detergent-labile cofactor' unresolved
    • Scaffolding of downstream components not yet demonstrated
  3. 1998 High

    Identification of MEK1/2 and ERK as direct KSR1-binding partners established KSR1 as a multi-component scaffold bridging RAF, MEK, and ERK, and explained how overexpression could inhibit signaling through stoichiometric titration of cascade members.

    Evidence Yeast two-hybrid and co-immunoprecipitation in COS-7 cells by two independent groups

    PMID:9427625 PMID:9427629

    Open questions at the time
    • Stoichiometry of the scaffold complex not determined
    • In vivo scaffold function not yet validated
  4. 1999 High

    Mass spectrometry-based phosphopeptide mapping revealed five in vivo phosphorylation sites on KSR1—two constitutive (Ser297, Ser392) mediating 14-3-3 binding and three RAS-inducible MAPK-consensus sites—demonstrating that KSR1 is itself an ERK substrate subject to feedback regulation.

    Evidence Mass spectrometry phosphopeptide identification, site-directed mutagenesis, MEK inhibitor treatment

    PMID:9858547

    Open questions at the time
    • Kinases responsible for constitutive phosphorylation not yet identified
    • Functional consequence of each site not fully dissected
  5. 2001 High

    Identification of C-TAK1 as the kinase that phosphorylates KSR1 Ser392 to create a 14-3-3 anchor site resolved how KSR1 is sequestered in the cytoplasm and how growth factor-induced dephosphorylation licenses membrane translocation.

    Evidence Co-immunoprecipitation, in vitro kinase assay, S392A mutagenesis, confocal imaging of membrane translocation

    PMID:11741534

    Open questions at the time
    • Phosphatase identity not yet known
    • Regulation of C-TAK1 activity itself unclear
  6. 2002 High

    Generation of KSR1-deficient mice proved that KSR1 functions as a bona fide scaffold in vivo: KSR1 loss attenuated ERK activation, blocked T-cell activation, and KSR1 was shown to independently bind RAF and MEK to promote their complex formation.

    Evidence KSR1 knockout mouse phenotyping, high-molecular-weight complex analysis, co-immunoprecipitation, in vitro kinase assays by two independent groups

    PMID:11850406 PMID:11940661

    Open questions at the time
    • Structural basis of scaffold assembly unknown
    • Relative contribution of scaffolding vs. allosteric activation unclear
  7. 2003 High

    Discovery that PP2A constitutively associates with KSR1 and dephosphorylates the 14-3-3 binding site upon growth factor signaling completed the phosphorylation–dephosphorylation switch model controlling KSR1 membrane recruitment.

    Evidence Mass spectrometry of KSR1 complex, co-immunoprecipitation, PP2A inhibition studies

    PMID:12932319

    Open questions at the time
    • Which PP2A regulatory subunit specifies KSR1 targeting not fully resolved
    • Adaptor linking PP2A to KSR1 not yet identified
  8. 2006 High

    CK2 was identified as a constitutive KSR1-associated kinase that facilitates RAF N-region phosphorylation, revealing that KSR1 scaffolds not only the core ERK cascade but also an upstream activating kinase for RAF.

    Evidence Mass spectrometry, co-immunoprecipitation, C1 domain mutagenesis, CK2 inhibitor treatment

    PMID:17174095

    Open questions at the time
    • Structural basis of CK2–C1 domain interaction not determined
    • Whether CK2 phosphorylates KSR1 itself not fully tested
  9. 2010 High

    Reconstitution with bacterially produced KSR1 demonstrated intrinsic serine kinase activity including autophosphorylation and MEK1 phosphorylation, resolving the long-standing debate about whether KSR1 is a true pseudokinase or retains catalytic function.

    Evidence Recombinant KSR1 in vitro kinase assay with active-site D683A/D700A mutants, TNF-induced apoptosis rescue

    PMID:21144847

    Open questions at the time
    • In vivo substrates of KSR1 kinase activity not comprehensively identified
    • Relative contribution of kinase vs. scaffold activity to signaling output unclear
  10. 2011 High

    The crystal structure of KSR2–MEK1 complex revealed how KSR binds MEK through activation-segment and αG-helix contacts and showed that BRAF allosterically activates KSR through side-to-side heterodimerization, providing the first atomic-level model of scaffold-mediated kinase cascade assembly.

    Evidence X-ray crystallography, in vitro kinase assays, chemical genetics, dimer-interface mutagenesis

    PMID:21441910

    Open questions at the time
    • Full-length KSR1 structure not available
    • Dynamic conformational changes during signaling not captured
  11. 2012 High

    NMR characterization of the CC-SAM domain showed it directly binds membranes via helix α3, identifying the structural determinant that targets KSR1 to the plasma membrane independently of the C1 domain.

    Evidence NMR spectroscopy, α3 mutagenesis, confocal imaging, in vitro micelle/bicelle binding

    PMID:23250398

    Open questions at the time
    • Lipid specificity of CC-SAM binding not defined
    • How CC-SAM and C1 domain cooperate in membrane targeting unclear
  12. 2014 Medium

    GEF-H1 was identified as the adaptor that bridges PP2A B′ subunits to KSR1 for Ser392 dephosphorylation, completing the molecular wiring of the positive feedback loop by which oncogenic RAS sustains KSR1 membrane recruitment.

    Evidence Co-immunoprecipitation, in vitro phosphatase assay, knockdown, xenograft assays

    PMID:24525234

    Open questions at the time
    • GEF-H1-independent mechanisms of PP2A-KSR1 interaction not excluded
    • In vivo validation in genetic models not performed
  13. 2016 High

    Structure-guided small molecules (APS-2-79) that stabilize an inactive KSR conformation demonstrated that KSR1's conformational state—not merely its presence—gates RAF heterodimerization and MEK phosphorylation, opening a pharmacological strategy to target the scaffold.

    Evidence Structure-guided compound design, RAF dimerization assays, MEK phosphorylation assays, cancer cell viability

    PMID:27556948

    Open questions at the time
    • In vivo pharmacokinetics and efficacy not reported
    • Selectivity over KSR2 not fully characterized
  14. 2018 High

    A higher-resolution structural study revealed that MEK binding to KSR1 asymmetrically drives BRAF-KSR1 heterodimerization through both kinase-domain and N-terminal (CC-SAM/BRS) contacts, establishing the complete allosteric mechanism by which the KSR1-MEK binary complex activates BRAF catalysis.

    Evidence Crystal structures, biochemical dimerization assays, co-immunoprecipitation, domain mutagenesis

    PMID:29433126

    Open questions at the time
    • Dynamics of the ternary complex in living cells not resolved
    • How KSR1 vs. KSR2 selectivity for RAF isoforms is achieved structurally
  15. 2020 High

    Crystal structures of KSR-MEK complexes with clinical MEK inhibitors (trametinib) showed that KSR remodels MEK's allosteric drug-binding pocket and that drug binding to the KSR-MEK interface disrupts RAF-MEK complexes, explaining drug mechanism and resistance phenomena.

    Evidence X-ray crystallography of KSR-MEK-inhibitor ternary complexes, kinetic binding assays, mutagenesis, cell signaling assays

    PMID:32927473

    Open questions at the time
    • Impact on clinical resistance mechanisms in patients not directly demonstrated
    • Structural effects of other MEK inhibitor classes not fully explored
  16. 2022 Medium

    Ectopic KSR1 activates the MAPK pathway and drives proliferation even in the absence of RAS proteins, provided at least one RAF family member is present for dimerization, demonstrating that KSR1-RAF dimerization is sufficient to initiate signaling independent of canonical RAS-GTP.

    Evidence RAS-null cell system, RAF/MEK knockout cells, KSR1 dimerization and ATP-binding mutants, proliferation assays

    PMID:35313064

    Open questions at the time
    • Physiological relevance of RAS-independent KSR1 activation unclear
    • Whether endogenous KSR1 levels achieve this in any tissue not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structure of KSR1 in its autoinhibited and active states, the precise in vivo substrates of KSR1's intrinsic kinase activity, and the quantitative contribution of kinase versus scaffold functions to ERK signaling output remain unresolved.
  • No full-length KSR1 structure available
  • In vivo kinase substrates beyond MEK1 not identified
  • Kinase-dead knock-in mouse not reported to separate catalytic from scaffold roles

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0140096 catalytic activity, acting on a protein 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 2 GO:0005768 endosome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2
Partners
BRAFCSNK2A1MAP2K1MAPK1MARK2PPP2CARAF1YWHAG
Complex memberships
KSR1-BRAF heterodimerKSR1-CK2 complexKSR1-MEK1/2 scaffold complexKSR1-PP2A complex

Evidence

Reading pass · 57 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 KSR (kinase suppressor of Ras) was identified as a novel protein kinase required for RAS signal transduction in Drosophila, functioning between RAS and RAF in receptor tyrosine kinase pathways, with mammalian homologs defining a novel class of kinases. Genetic screens, cloning, genetic epistasis Cell High 8521512 8521513 8521514
1995 C. elegans ksr-1 encodes a positive modifier of vulval induction acting downstream of or in parallel to let-60 ras, encoding a novel putative protein kinase related to the Raf family of Ser/Thr kinases. Genetic suppressor screen, epistasis analysis, cloning Cell High 8521513 8521514
1996 Murine KSR1 cooperates with activated Ras to promote MEK and MAPK activation, associates with Raf-1 at the plasma membrane in a Ras-dependent manner, and the isolated KSR kinase domain (C-terminal) suppresses Ras signaling, whereas the N-terminal domain cooperates with Ras. Xenopus oocyte maturation assay, cellular transformation assay, co-immunoprecipitation, subcellular fractionation Genes & development High 8946910
1997 KSR1 stimulates Raf-1 activity in a kinase-independent manner via its cysteine-rich CA3 domain, involving a detergent-labile cofactor, and translocates from cytoplasm to plasma membrane in the presence of activated Ras. In vitro kinase assay, domain mutagenesis, subcellular fractionation, Xenopus oocyte assay Proceedings of the National Academy of Sciences of the United States of America High 9371754
1997 KSR1 binds 14-3-3 proteins via multiple binding sites and forms a complex with Raf kinase specifically in the membrane fraction of cells; overexpression of KSR with 14-3-3 induced Xenopus oocyte maturation blocked by dominant-negative Raf-1. Yeast two-hybrid, co-immunoprecipitation, cell fractionation, Xenopus oocyte assay Current biology : CB High 9115393
1998 Mammalian KSR1 directly interacts with MEK1/2 via its C-terminal region and with ERK via its N-terminal region; KSR1 overexpression inhibits MAP kinase activation, consistent with a scaffold protein linking MEK and ERK. Yeast two-hybrid, co-immunoprecipitation in COS-7 cells, microinjection, dominant-negative analysis Current biology : CB High 9427625 9427629
1998 Murine KSR1 interacts with MEK-1 and MEK-2 by yeast two-hybrid and co-immunoprecipitation; the MEK subpopulation complexed with KSR1 displays no kinase activity, and KSR1 inhibits Ras-induced transformation, suggesting KSR can block MEK in an inactive form. Yeast two-hybrid, co-immunoprecipitation, transformation assay Current biology : CB High 9427625
1999 KSR1 contains five in vivo phosphorylation sites: two constitutive (Ser297, Ser392) mediating 14-3-3 binding, and three Ras-inducible (Thr260, Thr274, Ser443) matching MAPK consensus, with activated MAPK associating with KSR1 in a Ras-dependent manner, identifying KSR1 as an in vivo MAPK substrate. Mass spectrometry phosphopeptide mapping, site-directed mutagenesis, co-immunoprecipitation, MEK inhibitor treatment Molecular and cellular biology High 9858547
1999 KSR1 binds to G-protein betagamma subunits (gamma10, gamma2, gamma3) via its CA3 cysteine-rich domain, and this interaction mediates KSR1 translocation to the plasma membrane; KSR1 inhibits betaGamma-induced MAPK activation. Yeast two-hybrid, co-immunoprecipitation, pertussis toxin treatment, subcellular translocation assay The Journal of biological chemistry Medium 10075696
2000 B-KSR1, a brain-specific splice variant of KSR1, constitutively associates with MEK and inducibly interacts with activated MAPK in brain tissues; it promotes sustained MAPK activation and NGF-induced neuronal differentiation, and MEK binding requires the intact catalytic domain. Co-immunoprecipitation, Western blot, PC12 cell differentiation assay, mutagenesis of loss-of-function alleles Molecular and cellular biology Medium 10891492
2001 C-TAK1 constitutively associates with KSR1 and phosphorylates Ser392 to create a 14-3-3 binding site, sequestering KSR1 in the cytoplasm; in response to growth factor signaling, Ser392 phosphorylation is reduced, allowing KSR1 to translocate to the plasma membrane and colocalize with activated Ras and Raf-1. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, confocal microscopy, subcellular fractionation Molecular cell High 11741534
2002 KSR functions as a scaffold that assembles RAF/MEK complexes, facilitating phosphorylation of MEK by RAF. KSR associates independently with RAF and MEK, and these interactions promote RAF/MEK complex formation. KSR-deficient mice show attenuated ERK activation sufficient to block T-cell activation. KSR-deficient mouse generation, co-immunoprecipitation, high-molecular-weight complex analysis, in vitro kinase assay Molecular and cellular biology / Genes & development High 11850406 11940661
2002 The NMR solution structure of the KSR1 C1 domain reveals unique ligand-binding region and surface charge distribution distinct from Raf-1 and PKCgamma C1 domains; the KSR1 C1 domain does not bind phorbol esters or ceramide, does not interact with Ras, and is absolutely required for membrane localization of KSR1. NMR structure determination, chimeric protein analysis, lipid-binding assays, subcellular localization assay Journal of molecular biology High 11786023
2003 PP2A associates with KSR1: the enzymatic core subunits (PR65A and catalytic C) constitutively bind the N-terminal domain of KSR1, while the regulatory PR55B subunit binds upon growth factor treatment. PP2A dephosphorylates KSR1 (and Raf-1) on 14-3-3 binding sites, enabling KSR1 membrane recruitment and MAPK pathway activation. Mass spectrometry of KSR1-scaffolding complex, co-immunoprecipitation, PP2A inhibition, phosphorylation assays Current biology : CB High 12932319
2003 In C. elegans, PP2A phosphatase and PAR-1 kinase act downstream of Raf to positively and negatively regulate KSR activity, respectively; high Zn2+ concentration dramatically increases KSR phosphorylation in mammalian cells, targeting a specific step involving the KSR scaffold. Genetic double mutant analysis, biochemical phosphorylation assay in mammalian cells The EMBO journal Medium 14685271
2004 KSR1 phosphorylation at Ser392 and Thr274 regulates KSR1 protein stability, subcellular localization, and ERK activation; mutation of these sites (KSR1.TVSA) promotes sustained ERK activation, accelerated cell cycle progression, and increased KSR1 stability. Site-directed mutagenesis, cell proliferation assays, subcellular fractionation, Western blotting The Journal of biological chemistry Medium 15371409
2004 KSR1 regulates the intensity and duration of ERK activation to modulate proliferative and oncogenic potential; concentration-dependent effects reveal optimal KSR1 expression maximally associates with all Raf/MEK/ERK cascade members and mediates transformation. KSR1-/- mouse embryo fibroblasts, KSR1 re-expression at varying levels, Ras(V12) transformation assay, co-immunoprecipitation Molecular and cellular biology High 15121859
2004 LSP1 (leukocyte-specific protein 1), an F-actin binding protein, associates with KSR1, MEK1, and ERK2 and targets them to peripheral actin filaments, compartmentalizing the ERK/MAP kinase pathway at the cytoskeleton. Co-immunoprecipitation, confocal microscopy Journal of cell science Medium 15090600
2006 CK2 (casein kinase 2 holoenzyme) is a constitutive KSR1-binding partner requiring the basic surface of the KSR1 atypical C1 domain; CK2 bound to KSR1 facilitates ERK cascade signaling by acting as a Raf family N-region kinase, and disruption of KSR1/CK2 reduces growth-factor-induced phosphorylation of C-Raf and B-Raf. Mass spectrometry of KSR1 complex, co-immunoprecipitation, domain mutagenesis, CK2 inhibition, kinase phosphorylation assay Current biology : CB High 17174095
2006 In Drosophila, KSR induces RAF activation through its kinase-like domain by a mechanism independent of its scaffolding property or putative kinase activity; KSR is recruited to RAF prior to signal activation by CNK in association with a novel SAM domain-containing protein HYP. Genetic analysis, co-immunoprecipitation, domain mutagenesis in Drosophila Genes & development Medium 16600912
2007 KSR1 undergoes caspase-dependent cleavage during apoptosis, destroying its scaffolding function and generating a stable C-terminal fragment that inhibits ERK activation; cleavage correlates with reduced phosphoERK levels and occurs in vivo during mammary gland involution. Caspase cleavage assay, mutagenesis (cleavage-resistant DEVA-KSR1), Western blot, MEK inhibitor rescue The Journal of biological chemistry High 17613518
2008 14-3-3gamma specifically and functionally interacts with KSR1 via the C-terminal stretch of 14-3-3gamma; this binding protects KSR1 from EGF-induced dephosphorylation, impairs ERK2 activation, and acts as a cytosolic anchor keeping KSR1 inactive. 14-3-3gamma binds KSR1 as a monomer. In vitro binding assay, co-immunoprecipitation, RNAi, confocal microscopy, Xenopus oocyte assay The Journal of biological chemistry Medium 18426801
2008 IMP (E3 ubiquitin ligase) inhibits ERK cascade signaling by disrupting KSR1 homo-oligomerization and B-Raf/c-Raf hetero-oligomerization, thereby impairing MEK recruitment to activated Raf family members and c-Raf kinase activation. Co-immunoprecipitation, ubiquitin ligase assays, RNAi, protein complex analysis The Journal of biological chemistry Medium 18332145
2009 KSR1 is recruited to the immunological synapse during T-cell activation and to NK cell immunological synapses, and membrane recruitment of KSR1 is required for recruitment of active ERK to the synapse. KSR1 regulates the threshold for MAPK activation in T cells without altering the all-or-none nature of the response. KSR1-/- mice, live imaging/confocal microscopy, single-cell ERK activation analysis, NK cytolysis assay Molecular and cellular biology Medium 19139278 19188442
2009 KSR1 is required for cell cycle reinitiation following DNA damage; KSR1-/- cells cannot recover from MMC-induced G2/M arrest even after DNA damage repair, and a KSR1 mutant unable to bind ERK fails to rescue reinitiation, demonstrating the KSR1-ERK interaction is essential for this function. KSR1-/- MEFs, KSR1 re-expression, MMC treatment, cell cycle analysis, ERK binding-deficient mutant The Journal of biological chemistry Medium 19147494
2010 KSR1 is a functional protein kinase capable of serine autophosphorylation and direct phosphorylation of MEK1 in vitro; kinase-inactive KSR1 (D683A/D700A) lacks these activities, and both KSR1 kinase activity and MEK kinase activity are required for TNF-induced colon epithelial cell survival. Recombinant protein production in E. coli, in vitro kinase assay, autophosphorylation assay, MBP phosphorylation, TNF apoptosis assay Experimental cell research High 21144847
2011 Crystal structure of KSR2 kinase domain in complex with MEK1 reveals interactions mediated by activation segments and C-lobe αG helices; KSR2 self-associates via a side-to-side interface (analogous to BRAF); BRAF allosterically stimulates KSR2 kinase activity by heterodimerization, and KSR2-BRAF heterodimerization increases BRAF-induced MEK phosphorylation via relay of conformational signal from BRAF to release MEK activation segment. X-ray crystallography, in vitro kinase assay, chemical genetics, mutagenesis Nature High 21441910
2011 Most RAF inhibitors induce KSR1 binding to wild-type and oncogenic B-RAF (including V600E) requiring direct drug binding to B-RAF and conserved dimer interface residues; KSR1 competes with C-RAF for inhibitor-induced B-RAF binding, attenuating the paradoxical activating effect of RAF inhibitors on ERK signaling. Co-immunoprecipitation, dimer interface mutagenesis, ERK activation assays in cancer cell lines Current biology : CB High 21458265
2011 Feedback phosphorylation of KSR1 by ERK1/2 reduces KSR1 localization to dendritic spines; expression of feedback-deficient KSR1 promotes sustained ERK1/2 activation and potentiates excitatory postsynaptic currents in hippocampal neurons. Immunocytochemistry, confocal imaging, electrophysiological recordings, Western blot, mutagenesis FASEB journal Medium 21471251
2012 KSR1 contains a CC-SAM (coiled coil-sterile α motif) domain that targets KSR1 to specific signaling sites at the plasma membrane in growth factor-treated cells; membrane binding is mediated by helix α3 of the CC motif, and mutation of α3 residues abolishes plasma membrane targeting. NMR spectroscopy, mutagenesis, confocal microscopy, in vitro micelle/bicelle binding Science signaling High 23250398
2012 VRK2A anchors KSR1-MEK1 complexes to the endoplasmic reticulum (ER); VRK2A and KSR1 interact via their respective C-terminal regions, MEK1 independently contacts both KSR1 (CA5 region) and VRK2A N-terminus, forming a high molecular size complex (600-1000 kDa) that prevents ERK1/2 incorporation after EGF stimulation. Co-immunoprecipitation, subcellular fractionation, VRK2A knockdown, EGF stimulation assays Cellular and molecular life sciences : CMLS Medium 22752157
2013 AMPK phosphorylates BRAF at Ser729, promoting 14-3-3 binding and disrupting the BRAF-KSR1 interaction, leading to attenuation of MEK-ERK signaling and impaired keratinocyte proliferation. In vitro kinase assay, co-immunoprecipitation, mutagenesis, cell proliferation assays Molecular cell High 24095280
2014 KSR1 interacts with caveolin-1 and redistributes MEK and ERK to caveolin-1-rich fractions; a KSR1 mutant unable to interact with caveolin-1 fails to efficiently mediate growth factor-induced ERK activation at early stages, and abolishing the KSR1-caveolin-1 interaction impairs H-Ras(V12)-induced senescence and transformation. Co-immunoprecipitation, sucrose gradient fractionation, KSR1 mutagenesis, KSR1-/- MEF rescue, transformation assay Molecular and cellular biology Medium 25002533
2014 GEF-H1 acts as an adaptor linking PP2A B' subunits to KSR1 (independent of its RhoGEF activity), mediating dephosphorylation of KSR1 Ser392 and activation of MAPK signaling in a positive feedback loop for oncogenic RAS. Co-immunoprecipitation, in vitro phosphatase assay, knockdown/overexpression, xenograft assays Cancer cell Medium 24525234
2016 Small molecules (exemplified by APS-2-79) stabilize a previously unrecognized inactive state of KSR guided by KSR mutations that suppress oncogenic Ras signaling; these compounds antagonize RAF heterodimerization and conformational changes required for phosphorylation of KSR-bound MEK, and enhance MEK inhibitor potency in Ras-mutant cells. Structure-guided drug design based on KSR mutations, biochemical RAF dimerization assays, MEK phosphorylation assays, cell viability assays Nature High 27556948
2016 Praja2 is the E3 ubiquitin ligase that ubiquitylates KSR1, inducing its polyubiquitination and proteasomal degradation in response to receptor stimulation, thereby attenuating ERK1/2 signaling. Co-immunoprecipitation, ubiquitination assay, proteasome inhibition (MG132), knockdown/overexpression, stem cell pluripotency assay Cell death & disease Medium 27195677
2016 PKA phosphorylation of Rap1 (Ser180/Ser179) creates a 14-3-3 binding site that links Rap1 to the scaffold protein KSR1; because KSR1 and B-Raf exist as heterodimers, this also brings B-Raf to Rap1 to sustain ERK activation by cAMP. Co-immunoprecipitation, in vitro phosphorylation assay, mutagenesis, ERK activation assay in HEK293 cells The Journal of biological chemistry Medium 28003362
2017 Oncogenic RAS and BRAF induce perinuclear relocalization of KSR1, CK2, and p-ERK1/2 to endosomal compartments (perinuclear signaling complexes, PSCs); this requires endocytosis, MEK-ERK and CK2 kinase activities, and the presence of KSR1. KSR1-positive PSCs provide a platform for phosphorylation of the transcription factor C/EBPbeta. Confocal microscopy, Rab11 co-localization, MEK/CK2 inhibitors, KSR1 knockdown, C/EBPbeta phosphorylation assay Cancer research Medium 29259016
2018 MEK binding to the KSR1 kinase domain asymmetrically drives BRAF-KSR1 heterodimerization; KSR1 selective heterodimerization with BRAF is specified by direct contacts between N-terminal regulatory regions including the BRS domain in BRAF and the CC-SAM domain in KSR1; KSR-MEK complexes allosterically activate BRAF through N-terminal and kinase domain contacts. Crystal structure, biochemical dimerization assays, co-immunoprecipitation, in vitro kinase assay, domain mutagenesis Nature High 29433126
2018 Erbin interacts with KSR1 and displaces it from the RAF/MEK/ERK complex to prevent signal propagation; loss of Erbin increases amplitude and duration of RAS/RAF signaling via KSR1. Co-immunoprecipitation, KSR1 pulldown, knockdown, signaling assays, in vivo APC-KO mouse model Cancer research Medium 29980571
2020 X-ray crystal structures of MEK bound to KSR with MEK inhibitors including trametinib reveal that trametinib directly engages KSR at the MEK interface; KSR remodels the allosteric pocket of MEK, affecting drug binding and residence time; trametinib binding to KSR-MEK disrupts the related RAF-MEK complex through conserved interface residues. X-ray crystallography of KSR-MEK-inhibitor complexes, kinetic drug binding assays, mutagenesis, cell-based signaling assays Nature High 32927473
2021 Calmodulin binds directly to KSR1 in a Ca2+-dependent manner (in vitro and in cells); calmodulin antagonism impairs EGF-induced KSR1 translocation to the plasma membrane and reduces KSR1-ERK complex formation, thereby suppressing ERK activation. In vitro binding with purified proteins, co-immunoprecipitation, confocal microscopy, calmodulin inhibitor treatment The Journal of biological chemistry Medium 33766558
2021 KSR1 promotes epithelial-to-mesenchymal transition via preferential translation of EPSTI1 mRNA; KSR1-dependent induction of EPSTI1 drives the E- to N-cadherin switch and migratory/invasive behavior in colorectal cancer cells through ZEB1 and Slug transcriptional repressors. KSR1 disruption, ectopic EPSTI1 expression, migration/invasion assays, Western blot, polysome profiling eLife Medium 33970103
2021 PJA2 (praja2) ubiquitylates KSR1, reducing KSR1 protein stability; KDM5A inhibits PJA2 expression by removing H3K4me3 from the PJA2 promoter, thereby indirectly stabilizing KSR1 and promoting MAPK signaling and macrophage M2 polarization in gastric cancer. Dual luciferase reporter, ChIP assay, co-immunoprecipitation, cycloheximide chase, ubiquitination assay Journal of translational medicine Medium 34372882
2022 KSR1 ectopic expression activates the MAPK pathway and induces cell proliferation in the absence of RAS proteins but requires at least one RAF family member for dimerization and stimulation; KSR1 promotes translocation of heterodimerized RAF to the cell membrane; mutations in the DFG motif of KSR1 affecting ATP binding impair proliferation induction. RAS-null cell system, RAF/MEK knockout cells, KSR1 dimerization-deficient mutants, ATP-binding mutants, cell proliferation assays Molecular oncology Medium 35313064
2022 SHP2 interacts with KSR1 through its protein tyrosine phosphatase domain; activated SHP2 during adaptive MEK inhibitor resistance impairs SHP2-KSR1 interaction, activating KSR1 to promote MAPK signaling; a KSR1 activating mutation (S269A) diminishes the synergistic anti-proliferative effect of SHP2 inhibitor and MEK inhibitor combination. Co-immunoprecipitation, KSR1 knockdown, KSR1 activating mutation, ERK signaling assays, xenograft assays Cancer letters Medium 36493900
2016 KSR1 promotes translation of Myc protein by a posttranscriptional mechanism in colon tumor cells, supporting tumor cell survival alongside EPHB4-dependent elevation of Myc mRNA. KSR1 knockdown, ectopic re-expression, Western blot, mRNA quantification, survival assays Molecular and cellular biology Low 27273865
2011 KSR1 regulates KSR1-dependent control of PGC1α and ERRα expression to promote metabolic capacity required for oncogenic H-Ras(V12)-induced anchorage-independent growth, independent of ERK signaling. KSR1-/- MEFs, ectopic PGC1α/ERRα expression, anchorage-independent growth assay, ERRα inhibitor treatment Molecular and cellular biology Medium 21518958
2011 KSR1 loss in IL-10-deficient mice causes exacerbated colitis due to dysregulated IFN-γ production in T lymphocytes; KSR1 expressed in hematopoietic lineages is protective, and KSR1 deficiency increases Th1 polarization while impairing Th17 polarization. KSR1-/- IL10-/- double KO mice, bone marrow transplant, in vitro Th1/Th17 polarization assay, IFN-γ neutralizing antibody treatment Gastroenterology Medium 20875416
2005 KSR1 coordinates ERK and RSK activation with C/EBPbeta synthesis during adipogenesis; KSR1 deletion prevents adipogenesis in vitro, and appropriate KSR1 levels promote phosphorylation and stabilization of C/EBPbeta at a specific moment in the adipogenic program, while elevated KSR1 inhibits adipogenesis via high sustained ERK phosphorylating PPARγ. KSR1-/- cells, KSR1 re-expression at graded levels, adipocyte differentiation assay, ERK/RSK activation measurement Molecular and cellular biology Medium 16107706
2011 KSR1 is required for efficient NK-mediated cytolysis and cytolytic granule polarization; KSR1 is recruited to the immunological synapse and membrane recruitment of KSR1 is required for ERK localization to the synapse. KSR1-/- mice, NK cytolysis assay, confocal imaging of immunological synapse Molecular and cellular biology Medium 19139278
2011 KSR1 regulates BRCA1 degradation in breast cancer cells; KSR1 stabilizes BRCA1 protein levels by reducing BRCA1 ubiquitination through increasing BARD1 abundance. KSR1 overexpression, ubiquitination assay, BRCA1/BARD1 Western blot, xenograft assay Oncogene Low 24909178
2011 KSR1 regulates FLIP protein levels post-translationally in endometrial carcinoma cells; KSR1 silencing down-regulates FLIP by promoting FADD-dependent inhibition of FLIP translation after TRAIL stimulation, sensitizing cells to TRAIL- and Fas-induced apoptosis. KSR1 shRNA knockdown, KSR1 re-expression, apoptosis assay, translational regulation assay The American journal of pathology Low 21435442
2013 KSR1 decreases DBC1 phosphorylation, reducing the DBC1-SIRT1 interaction; this enables SIRT1 to deacetylate p53, thereby inhibiting p53 transcriptional activity. SILAC mass spectrometry phosphoproteomics, co-immunoprecipitation, luciferase reporter assay, Western blot British journal of cancer Medium 24129246
2016 DiRas3 binds to KSR1 independently of activated Ras and RAF; depending on local stoichiometry, DiRas3 can either enhance KSR1 homodimerization or recruit KSR1 to the Ras:C-RAF complex, thereby reducing C-RAF availability for B-RAF heterodimerization. Co-immunoprecipitation, dimerization assays, mutagenesis Cellular signalling Low 27368419
2011 MARK2 (related to C-TAK1) binds and phosphorylates KSR1 on Ser392 in vivo; genetic deletion of KSR1 in MARK2-/- mice reverses the increased insulin sensitivity caused by MARK2 loss, placing KSR1 downstream of MARK2 in insulin-regulated glucose metabolism. Double KO mice (mark2-/- ksr1-/-), glucose tolerance test, co-immunoprecipitation, in vitro phosphorylation assay PloS one Medium 22206009
2024 KSR1 knockout mice are resistant to cisplatin- and noise-induced hearing loss; loss of KSR1 reduces BRAF/MEK/ERK phosphorylation cascade in cochlear cells following insults; dabrafenib (BRAF inhibitor) does not enhance protection in KO mice, placing KSR1 upstream of BRAF in cochlear MAPK injury signaling. KSR1 germline KO mice, ABR hearing testing, BRAF inhibitor treatment, cochlear MAPK phosphorylation assay The Journal of neuroscience Medium 38548338

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 KSR, a novel protein kinase required for RAS signal transduction. Cell 331 8521512
1995 The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction. Cell 259 8521513
2003 Protein phosphatase 2A positively regulates Ras signaling by dephosphorylating KSR1 and Raf-1 on critical 14-3-3 binding sites. Current biology : CB 255 12932319
1995 The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans. Cell 248 8521514
2001 C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1. Molecular cell 242 11741534
2002 Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo. Molecular and cellular biology 230 11940661
1996 KSR modulates signal propagation within the MAPK cascade. Genes & development 218 8946910
2011 A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK. Nature 210 21441910
2001 KSR: a MAPK scaffold of the Ras pathway? Journal of cell science 193 11309192
2002 KSR is a scaffold required for activation of the ERK/MAPK module. Genes & development 184 11850406
1999 Identification of constitutive and ras-inducible phosphorylation sites of KSR: implications for 14-3-3 binding, mitogen-activated protein kinase binding, and KSR overexpression. Molecular and cellular biology 174 9858547
1998 Regulation of the MAP kinase pathway by mammalian Ksr through direct interaction with MEK and ERK. Current biology : CB 170 9427629
1997 The protein kinase KSR interacts with 14-3-3 protein and Raf. Current biology : CB 150 9115393
1997 KSR stimulates Raf-1 activity in a kinase-independent manner. Proceedings of the National Academy of Sciences of the United States of America 143 9371754
2020 Structural basis for the action of the drug trametinib at KSR-bound MEK. Nature 135 32927473
1998 Murine Ksr interacts with MEK and inhibits Ras-induced transformation. Current biology : CB 131 9427625
2004 The molecular scaffold KSR1 regulates the proliferative and oncogenic potential of cells. Molecular and cellular biology 127 15121859
2007 KSR and CNK: two scaffolds regulating RAS-mediated RAF activation. Oncogene 118 17496912
2013 Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 association and cell proliferation. Molecular cell 115 24095280
2018 MEK drives BRAF activation through allosteric control of KSR proteins. Nature 109 29433126
2002 C. elegans ksr-1 and ksr-2 have both unique and redundant functions and are required for MPK-1 ERK phosphorylation. Current biology : CB 90 11882296
1998 The kinase suppressor of Ras (KSR) modulates growth factor and Ras signaling by uncoupling Elk-1 phosphorylation from MAP kinase activation. The EMBO journal 87 9501093
2014 The RhoGEF GEF-H1 is required for oncogenic RAS signaling via KSR-1. Cancer cell 84 24525234
2016 Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling. Nature 82 27556948
2006 CK2 Is a component of the KSR1 scaffold complex that contributes to Raf kinase activation. Current biology : CB 77 17174095
2002 Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR). Journal of molecular biology 75 11786023
2000 Identification of B-KSR1, a novel brain-specific isoform of KSR1 that functions in neuronal signaling. Molecular and cellular biology 70 10891492
2011 RAF inhibitor-induced KSR1/B-RAF binding and its effects on ERK cascade signaling. Current biology : CB 68 21458265
2005 The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis. Molecular and cellular biology 67 16107706
2004 Phosphorylation regulates KSR1 stability, ERK activation, and cell proliferation. The Journal of biological chemistry 63 15371409
2003 Modulation of KSR activity in Caenorhabditis elegans by Zn ions, PAR-1 kinase and PP2A phosphatase. The EMBO journal 55 14685271
2016 MicroRNA-497 inhibits tumor growth and increases chemosensitivity to 5-fluorouracil treatment by targeting KSR1. Oncotarget 50 26673620
2006 A KSR/CNK complex mediated by HYP, a novel SAM domain-containing protein, regulates RAS-dependent RAF activation in Drosophila. Genes & development 48 16600912
1999 KSR-1 binds to G-protein betagamma subunits and inhibits beta gamma-induced mitogen-activated protein kinase activation. The Journal of biological chemistry 47 10075696
2005 The rationale for deltanoids in therapy for myeloid leukemia: role of KSR-MAPK-C/EBP pathway. The Journal of steroid biochemistry and molecular biology 45 16046262
2016 Phosphorylation of Rap1 by cAMP-dependent Protein Kinase (PKA) Creates a Binding Site for KSR to Sustain ERK Activation by cAMP. The Journal of biological chemistry 43 28003362
2011 Kinase suppressor of ras 1 (KSR1) regulates PGC1α and estrogen-related receptor α to promote oncogenic Ras-dependent anchorage-independent growth. Molecular and cellular biology 42 21518958
2021 ELK4 promotes the development of gastric cancer by inducing M2 polarization of macrophages through regulation of the KDM5A-PJA2-KSR1 axis. Journal of translational medicine 41 34372882
2008 The Caenorhabditis elegans ekl (enhancer of ksr-1 lethality) genes include putative components of a germline small RNA pathway. Genetics 38 18245826
2013 The dual function of KSR1: a pseudokinase and beyond. Biochemical Society transactions 36 23863182
2009 KSR1 modulates the sensitivity of mitogen-activated protein kinase pathway activation in T cells without altering fundamental system outputs. Molecular and cellular biology 36 19188442
2004 Leukocyte-specific protein 1 targets the ERK/MAP kinase scaffold protein KSR and MEK1 and ERK2 to the actin cytoskeleton. Journal of cell science 36 15090600
2004 Kinase suppressor of RAS (KSR) amplifies the differentiation signal provided by low concentrations 1,25-dihydroxyvitamin D3. Journal of cellular physiology 33 14755538
2012 A CC-SAM, for coiled coil-sterile α motif, domain targets the scaffold KSR-1 to specific sites in the plasma membrane. Science signaling 32 23250398
2009 Proteomic characterization of the dynamic KSR-2 interactome, a signaling scaffold complex in MAPK pathway. Biochimica et biophysica acta 32 19563921
2017 KSR as a therapeutic target for Ras-dependent cancers. Expert opinion on therapeutic targets 29 28333549
2016 KSR1 and EPHB4 Regulate Myc and PGC1β To Promote Survival of Human Colon Tumors. Molecular and cellular biology 28 27273865
2012 VRK2 anchors KSR1-MEK1 to endoplasmic reticulum forming a macromolecular complex that compartmentalizes MAPK signaling. Cellular and molecular life sciences : CMLS 28 22752157
2011 KSR1 is overexpressed in endometrial carcinoma and regulates proliferation and TRAIL-induced apoptosis by modulating FLIP levels. The American journal of pathology 28 21435442
2008 The functional interaction of 14-3-3 proteins with the ERK1/2 scaffold KSR1 occurs in an isoform-specific manner. The Journal of biological chemistry 28 18426801
2023 SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status. Proceedings of the National Academy of Sciences of the United States of America 27 37972068
2022 KSR induces RAS-independent MAPK pathway activation and modulates the efficacy of KRAS inhibitors. Molecular oncology 27 35313064
2018 Erbin Suppresses KSR1-Mediated RAS/RAF Signaling and Tumorigenesis in Colorectal Cancer. Cancer research 26 29980571
2006 Induction of kinase suppressor of RAS-1(KSR-1) gene by 1, alpha25-dihydroxyvitamin D3 in human leukemia HL60 cells through a vitamin D response element in the 5'-flanking region. Oncogene 26 16732322
2017 The use of KnockOut serum replacement (KSR) in three dimensional rat testicular cells co-culture model: An improved male reproductive toxicity testing system. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 25 28478099
2016 praja2 regulates KSR1 stability and mitogenic signaling. Cell death & disease 25 27195677
2015 Ginkgo biloba extract enhances chemotherapy sensitivity and reverses chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells. Oncology reports 25 25962735
2010 KSR1 protects from interleukin-10 deficiency-induced colitis in mice by suppressing T-lymphocyte interferon-γ production. Gastroenterology 25 20875416
2022 The mechanism of activation of MEK1 by B-Raf and KSR1. Cellular and molecular life sciences : CMLS 24 35508574
2014 Caveolin-1 is required for kinase suppressor of Ras 1 (KSR1)-mediated extracellular signal-regulated kinase 1/2 activation, H-RasV12-induced senescence, and transformation. Molecular and cellular biology 24 25002533
2002 KSR--a regulator and scaffold protein of the MAPK pathway. Science's STKE : signal transduction knowledge environment 24 12060787
2004 Inflammatory bowel disease reveals the kinase activity of KSR1. The Journal of clinical investigation 22 15520853
2002 MAP kinase module: the Ksr connection. Current biology : CB 22 12007434
2011 Complexity in KSR function revealed by Raf inhibitor and KSR structure studies. Small GTPases 19 22292131
2010 KSR1 is a functional protein kinase capable of serine autophosphorylation and direct phosphorylation of MEK1. Experimental cell research 19 21144847
2009 The mitogen-activated protein kinase scaffold KSR1 is required for recruitment of extracellular signal-regulated kinase to the immunological synapse. Molecular and cellular biology 19 19139278
2008 IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. The Journal of biological chemistry 19 18332145
1983 Sibship with 17-ketosteroid reductase (17-KSR) deficiency and hypothyroidism. Lack of linkage of histocompatibility leucocyte antigen and 17-KSR loci. The Journal of clinical endocrinology and metabolism 19 6574136
2021 Calmodulin influences MAPK signaling by binding KSR1. The Journal of biological chemistry 18 33766558
2011 Compartmentalization of the MAPK scaffold protein KSR1 modulates synaptic plasticity in hippocampal neurons. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 21471251
2021 KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition. eLife 17 33970103
2013 SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1. British journal of cancer 17 24129246
2015 The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin-deficient tumors. Oncogene 16 26549023
2022 Sulfated alginate oligosaccharide exerts antitumor activity and autophagy induction by inactivating MEK1/ERK/mTOR signaling in a KSR1-dependent manner in osteosarcoma. Oncogenesis 15 35418575
2009 KSR1 is required for cell cycle reinitiation following DNA damage. The Journal of biological chemistry 15 19147494
2006 KSR regulation of the Raf-MEK-ERK cascade. Methods in enzymology 15 16757327
2017 Oncogenic RAS-Induced Perinuclear Signaling Complexes Requiring KSR1 Regulate Signal Transmission to Downstream Targets. Cancer research 14 29259016
2014 KSR1 regulates BRCA1 degradation and inhibits breast cancer growth. Oncogene 14 24909178
2014 KSR-based medium improves the generation of high-quality mouse iPS cells. PloS one 14 25171101
2013 Terbinafine inhibits KSR1 and suppresses Raf-MEK-ERK signaling in oral squamous cell carcinoma cells. Neoplasma 14 23581412
2012 Pravastatin normalizes ET-1-induced contraction in the aorta of type 2 diabetic OLETF rats by suppressing the KSR1/ERK complex. American journal of physiology. Heart and circulatory physiology 14 22886408
2011 Regulation of glucose homeostasis by KSR1 and MARK2. PloS one 14 22206009
2007 Caspase-dependent cleavage disrupts the ERK cascade scaffolding function of KSR1. The Journal of biological chemistry 14 17613518
2006 Ras-sensitive IMP modulation of the Raf/MEK/ERK cascade through KSR1. Methods in enzymology 14 16757328
2023 Analysis of RAS and drug induced homo- and heterodimerization of RAF and KSR1 proteins in living cells using split Nanoluc luciferase. Cell communication and signaling : CCS 13 37316874
2022 SHP2 inhibition mitigates adaptive resistance to MEK inhibitors in KRAS-mutant gastric cancer through the suppression of KSR1 activity. Cancer letters 13 36493900
2017 Metabolic stress regulates ERK activity by controlling KSR-RAF heterodimerization. EMBO reports 13 29263201
2012 Application of K/Sr co-doped calcium polyphosphate bioceramic as scaffolds for bone substitutes. Journal of materials science. Materials in medicine 13 22311075
2024 KSR1 Knockout Mouse Model Demonstrates MAPK Pathway's Key Role in Cisplatin- and Noise-induced Hearing Loss. The Journal of neuroscience : the official journal of the Society for Neuroscience 12 38548338
2024 Step-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans. PLoS pathogens 12 39213436
2021 Praja2 suppresses the growth of gastric cancer by ubiquitylation of KSR1 and inhibiting MEK-ERK signal pathways. Aging 12 33461174
2008 Downregulation of KSR1 in pancreatic cancer xenografts by antisense oligonucleotide correlates with tumor drug uptake. Cancer biology & therapy 12 18719367
2004 The kinase activity of kinase suppressor of Ras1 (KSR1) is independent of bound MEK. The Journal of biological chemistry 12 15084597
2023 Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells. International journal of molecular sciences 9 37511580
2011 Simulating EGFR-ERK signaling control by scaffold proteins KSR and MP1 reveals differential ligand-sensitivity co-regulated by Cbl-CIN85 and endophilin. PloS one 9 21829671
2015 KSR1 is coordinately regulated with Notch signaling and oxidative phosphorylation in thyroid cancer. Journal of molecular endocrinology 8 25608512
2015 Proteomic profile of KSR1-regulated signalling in response to genotoxic agents in breast cancer. Breast cancer research and treatment 8 26022350
2018 Homozygous KSR1 deletion attenuates morbidity but does not prevent tumor development in a mouse model of RAS-driven pancreatic cancer. PloS one 6 29596465
2016 Stabilization of C-RAF:KSR1 complex by DiRas3 reduces availability of C-RAF for dimerization with B-RAF. Cellular signalling 6 27368419
2002 Effects of prenyl pyrophosphates on the binding of S-Ras proteins with KSR. The Journal of experimental zoology 6 12410604