Gene Symbol: ksr
Description: kinase suppressor of ras
Alias: CG2899, Dmel\CG2899, EC3-1, EK3-1, KSR, KSR-1, Ksr, Ksr-1, SR3-1, dKsr, l(3)j5E2, kinase suppressor of ras, CG2899-PA, CG2899-PB, CG2899-PC, CG2899-PD, kinase suppressor of Ras, kinase suppressor of Ras85D, ksr-PA, ksr-PB, ksr-PC, ksr-PD, suppressor of Ras1 3-1
Species: fruit fly

Top Publications

  1. Garrington T, Johnson G. Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol. 1999;11:211-8 pubmed
    ..As new MAPK members are defined, determining their organization in kinase modules will be critical in understanding their select role in cellular regulation. ..
  2. Karim F, Chang H, Therrien M, Wassarman D, Laverty T, Rubin G. A screen for genes that function downstream of Ras1 during Drosophila eye development. Genetics. 1996;143:315-29 pubmed
    ..At least two suppressors appear to function either between Ras1 and Raf or in parallel to Raf. ..
  3. Roy F, Laberge G, Douziech M, Ferland McCollough D, Therrien M. KSR is a scaffold required for activation of the ERK/MAPK module. Genes Dev. 2002;16:427-38 pubmed
    ..Several proteins are suspected to play critical roles in this process. One of these is Kinase Suppressor of Ras (KSR), a component previously identified in RAS-dependent genetic screens in Drosophila and ..
  4. Anselmo A, Bumeister R, Thomas J, White M. Critical contribution of linker proteins to Raf kinase activation. J Biol Chem. 2002;277:5940-3 pubmed
    ..These proteins, KSR, CNK, and Sur-8, can interact with multiple core components of the Ras/MAP kinase cascade and may contribute to the ..
  5. Therrien M, Morrison D, Wong A, Rubin G. A genetic screen for modifiers of a kinase suppressor of Ras-dependent rough eye phenotype in Drosophila. Genetics. 2000;156:1231-42 pubmed
    b>kinase suppressor of Ras (ksr) encodes a putative protein kinase that by genetic criteria appears to function downstream of RAS in multiple receptor tyrosine kinase (RTK) pathways...
  6. Morrison D. KSR: a MAPK scaffold of the Ras pathway?. J Cell Sci. 2001;114:1609-12 pubmed
    b>Kinase Suppressor of Ras (KSR) is an intriguing component of the Ras pathway that was first identified by genetic studies performed in Drosophila melanogaster and Caenorhabditis elegans...
  7. Macagno J, Díaz Vera J, Yu Y, MacPherson I, Sandilands E, Palmer R, et al. FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells. PLoS Genet. 2014;10:e1004262 pubmed publisher
    ..Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours. ..
  8. Stark F, Pfannstiel J, Klaiber I, Raabe T. Protein kinase CK2 links polyamine metabolism to MAPK signalling in Drosophila. Cell Signal. 2011;23:876-82 pubmed publisher
    ..process not only requiring the core components Raf, MEK and Erk, but also many proteins like the scaffold protein KSR and several kinases to specifically localize, modulate and fine-tune the outcome of the pathway in a cell context ..
  9. Rajakulendran T, Sahmi M, Lefrancois M, Sicheri F, Therrien M. A dimerization-dependent mechanism drives RAF catalytic activation. Nature. 2009;461:542-5 pubmed publisher
    ..Moreover, we find that the RAF-related pseudo-kinase KSR (kinase suppressor of Ras) also participates in forming side-to-side heterodimers with RAF and can thereby trigger RAF activation...

More Information


  1. Douziech M, Roy F, Laberge G, Lefrancois M, Armengod A, Therrien M. Bimodal regulation of RAF by CNK in Drosophila. EMBO J. 2003;22:5068-78 pubmed
    Connector enhancer of KSR (CNK) is a multidomain-containing protein previously identified as a positive regulator of the RAS/MAPK pathway in Drosophila...
  2. Li W, Skoulakis E, Davis R, Perrimon N. The Drosophila 14-3-3 protein Leonardo enhances Torso signaling through D-Raf in a Ras 1-dependent manner. Development. 1997;124:4163-71 pubmed
    ..The effect of leo requires D-Raf and Ras1 activities but not KSR or DOS, two recently identified essential components of Drosophila RTK signaling pathways...
  3. Therrien M, Wong A, Rubin G. CNK, a RAF-binding multidomain protein required for RAS signaling. Cell. 1998;95:343-53 pubmed
    b>Kinase suppressor of ras (ksr) is required for efficient signal transmission within the RAS/MAPK cascade...
  4. Jacobs D, Glossip D, Xing H, Muslin A, Kornfeld K. Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. Genes Dev. 1999;13:163-75 pubmed
    ..These findings enabled us to predict new ERK substrates and design peptide inhibitors of ERK that functioned in vitro and in vivo. ..
  5. Douziech M, Sahmi M, Laberge G, Therrien M. A KSR/CNK complex mediated by HYP, a novel SAM domain-containing protein, regulates RAS-dependent RAF activation in Drosophila. Genes Dev. 2006;20:807-19 pubmed
    ..Here, we show that the scaffold KSR (kinase suppressor of RAS), a RAF homolog known to assemble RAF/MEK/ERK complexes, induces RAF activation in Drosophila by a ..
  6. Cabernard C, Affolter M. Distinct roles for two receptor tyrosine kinases in epithelial branching morphogenesis in Drosophila. Dev Cell. 2005;9:831-42 pubmed
    ..Ras and the Mapk pathway are also needed for Egf-regulated cell division/survival, but Pointed is dispensable. ..
  7. Benton R, St Johnston D. Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells. Cell. 2003;115:691-704 pubmed
    ..Thus, antagonism of Bazooka by PAR-1/14-3-3 may represent a general mechanism for establishing complementary cortical domains in polarized cells. ..
  8. Xu J, Hopkins K, Sabin L, Yasunaga A, Subramanian H, Lamborn I, et al. ERK signaling couples nutrient status to antiviral defense in the insect gut. Proc Natl Acad Sci U S A. 2013;110:15025-30 pubmed publisher
    ..These studies demonstrate that ERK signaling has a broadly antiviral role in insects and suggest that insects take advantage of cross-species signals in the meal to trigger antiviral immunity. ..
  9. Koveal D, Schuh Nuhfer N, Ritt D, Page R, Morrison D, Peti W. A CC-SAM, for coiled coil-sterile ? motif, domain targets the scaffold KSR-1 to specific sites in the plasma membrane. Sci Signal. 2012;5:ra94 pubmed publisher
    b>Kinase suppressor of Ras-1 (KSR-1) is an essential scaffolding protein that coordinates the assembly of the mitogen-activated protein kinase (MAPK) module, consisting of the MAPK kinase kinase Raf, the MAPK kinase MEK (mitogen-activated ..
  10. Karim F, Rubin G. Ectopic expression of activated Ras1 induces hyperplastic growth and increased cell death in Drosophila imaginal tissues. Development. 1998;125:1-9 pubmed
    ..Loss-of-function mutations in the genes encoding RAF, MEK, MAPK and KSR dominantly suppress RAS1V12-induced cell proliferation...
  11. Lai Z, Fetchko M, Li Y. Repression of Drosophila photoreceptor cell fate through cooperative action of two transcriptional repressors Yan and Tramtrack. Genetics. 1997;147:1131-7 pubmed
    ..Reduction of either yan or ttk activity suppresses eye phenotypes of the kinase suppressor of ras (ksr) gene mutation, which is consistent with the involvement of yan and ttk in the Ras/MAPK pathway.
  12. Claperon A, Therrien M. KSR and CNK: two scaffolds regulating RAS-mediated RAF activation. Oncogene. 2007;26:3143-58 pubmed
    ..elegans, we present two such proteins, the kinase suppressor of RAS (KSR) and connector enhancer of KSR (CNK) scaffolds, and highlight their implication in a novel mechanism ..
  13. Rubin G, Chang H, Karim F, Laverty T, Michaud N, Morrison D, et al. Signal transduction downstream from Ras in Drosophila. Cold Spring Harb Symp Quant Biol. 1997;62:347-52 pubmed
  14. Barbash D, Siino D, Tarone A, Roote J. A rapidly evolving MYB-related protein causes species isolation in Drosophila. Proc Natl Acad Sci U S A. 2003;100:5302-7 pubmed publisher
    ..Our results suggest that hybrid lethality may result from disruptions in gene regulation, and we also propose that rapid evolution may be a hallmark of speciation genes in general...
  15. Huang A, Rubin G. A misexpression screen identifies genes that can modulate RAS1 pathway signaling in Drosophila melanogaster. Genetics. 2000;156:1219-30 pubmed
    ..b>Kinase suppressor of Ras (KSR) functions genetically downstream of RAS1 in this signal transduction cascade...
  16. Zhang W, Thompson B, Hietakangas V, Cohen S. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila. PLoS Genet. 2011;7:e1002429 pubmed publisher
    ..The MAPK/ERK pathway acts via the ETS-1 transcription factor Pointed. This mechanism permits physiological adjustment of insulin sensitivity and subsequent maintenance of circulating glucose at appropriate levels. ..
  17. Karim F, Rubin G. PTP-ER, a novel tyrosine phosphatase, functions downstream of Ras1 to downregulate MAP kinase during Drosophila eye development. Mol Cell. 1999;3:741-50 pubmed
    ..PTP-ER binds to and inactivates Drosophila ERK/MAPK; however, it is unable to dephosphorylate and downregulate Drosophila MAPKSevenmaker. Resistance to PTP-ER activity partially accounts for the Sevenmaker mutant phenotype. ..
  18. Therrien M, Chang H, Solomon N, Karim F, Wassarman D, Rubin G. KSR, a novel protein kinase required for RAS signal transduction. Cell. 1995;83:879-88 pubmed
    ..The other encodes a protein kinase that we have named kinase suppressor of ras (ksr). By genetic criteria, we show that KSR functions in multiple receptor tyrosine kinase pathways...
  19. Therrien M, Michaud N, Rubin G, Morrison D. KSR modulates signal propagation within the MAPK cascade. Genes Dev. 1996;10:2684-95 pubmed
    b>Kinase suppressor of Ras (KSR) is a recently identified component of Ras-dependent signaling pathways...
  20. Roignant J, Hamel S, Janody F, Treisman J. The novel SAM domain protein Aveugle is required for Raf activation in the Drosophila EGF receptor signaling pathway. Genes Dev. 2006;20:795-806 pubmed publisher
    ..a sterile alpha motif (SAM) domain that can physically interact with the scaffold protein connector enhancer of Ksr (Cnk)...
  21. Johnson Hamlet M, Perkins L. Analysis of corkscrew signaling in the Drosophila epidermal growth factor receptor pathway during myogenesis. Genetics. 2001;159:1073-87 pubmed
    ..activity relative to the EGFR, spitz (spi), rhomboid (rho), daughter of sevenless (DOS), kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin...
  22. Cacace A, Michaud N, Therrien M, Mathes K, Copeland T, Rubin G, et al. Identification of constitutive and ras-inducible phosphorylation sites of KSR: implications for 14-3-3 binding, mitogen-activated protein kinase binding, and KSR overexpression. Mol Cell Biol. 1999;19:229-40 pubmed
    Genetic and biochemical studies have identified kinase suppressor of Ras (KSR) to be a conserved component of Ras-dependent signaling pathways...
  23. Ishimaru S, Williams R, Clark E, Hanafusa H, Gaul U. Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1. EMBO J. 1999;18:145-55 pubmed