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A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK

Author

Listed:
  • Damian F. Brennan

    (Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK)

  • Arvin C. Dar

    (University of California San Francisco)

  • Nicholas T. Hertz

    (University of California San Francisco)

  • William C. H. Chao

    (Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK)

  • Alma L. Burlingame

    (University of California San Francisco)

  • Kevan M. Shokat

    (University of California San Francisco)

  • David Barford

    (Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK)

Abstract

Allostery in kinase suppressor of RAS The RAS–RAF–MEK–ERK signalling pathway is important in the regulation of cell proliferation and is often aberrantly activated in cancer. KSR (kinase suppressor of RAS) is essential for RAS signaling, but its mechanism of action has been unclear. It is a member of the protein kinase family but was thought to be a pseudokinase with only scaffold functions. Structural and biochemical studies now reveal that KSR can function as a kinase, and by forming a heterodimer with BRAF, it relays an activating signal to MEK. This work points to KSR as a potential drug target in the RAS–ERK signalling pathway.

Suggested Citation

  • Damian F. Brennan & Arvin C. Dar & Nicholas T. Hertz & William C. H. Chao & Alma L. Burlingame & Kevan M. Shokat & David Barford, 2011. "A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK," Nature, Nature, vol. 472(7343), pages 366-369, April.
    • Handle: RePEc:nat:nature:v:472:y:2011:i:7343:d:10.1038_nature09860
    DOI: 10.1038/nature09860
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    Cited by:

    1. Yuji Kubota & Yuko Fujioka & Ashwini Patil & Yusuke Takagi & Daisuke Matsubara & Masatomi Iijima & Isao Momose & Ryosuke Naka & Kenta Nakai & Nobuo N. Noda & Mutsuhiro Takekawa, 2022. "Qualitative differences in disease-associated MEK mutants reveal molecular signatures and aberrant signaling-crosstalk in cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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