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Gene Review

cnk  -  connector enhancer of ksr

Drosophila melanogaster

Synonyms: CG6556, CNK, Cnk, Dmel\CG6556, EK2-3, ...
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High impact information on cnk

  • Src42 binding activity regulates Drosophila RAF by a novel CNK-dependent derepression mechanism [1].
  • Strikingly, we found that several cnk loss-of-function alleles have mutations clustered in this area and provide evidence that these mutations impair Src42 binding [1].
  • Our data are consistent with a model in which CNK promotes Raf phosphorylation/activation through membrane localization, oligomerization, or association with an activating kinase [2].
  • Connector enhancer of Ksr (CNK) is a conserved multidomain protein essential for Ras signaling in Drosophila melanogaster and thought to be involved in Raf kinase activation [2].
  • CNK is required for membrane recruitment of Raf, while KSR is likely required to couple Raf to upstream kinases [3].

Regulatory relationships of cnk

  • Unexpectedly, we also report that the C-terminal region of CNK contains a short bipartite element that strongly inhibits RAF catalytic function [4].

Other interactions of cnk

  • These proteins, KSR, CNK, and Sur-8, can interact with multiple core components of the Ras/MAP kinase cascade and may contribute to the structural organization of this cascade [3].


  1. Src42 binding activity regulates Drosophila RAF by a novel CNK-dependent derepression mechanism. Laberge, G., Douziech, M., Therrien, M. EMBO J. (2005) [Pubmed]
  2. Caenorhabditis elegans CNK-1 promotes Raf activation but is not essential for Ras/Raf signaling. Rocheleau, C.E., Rönnlund, A., Tuck, S., Sundaram, M.V. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Critical contribution of linker proteins to Raf kinase activation. Anselmo, A.N., Bumeister, R., Thomas, J.M., White, M.A. J. Biol. Chem. (2002) [Pubmed]
  4. Bimodal regulation of RAF by CNK in Drosophila. Douziech, M., Roy, F., Laberge, G., Lefrançois, M., Armengod, A.V., Therrien, M. EMBO J. (2003) [Pubmed]
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