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Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...

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Integrating signals from RTKs to ERK/MAPK.

Oncogene·2007
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C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1.

Molecular cell·2001
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Raf-1 without MEK?

Science's STKE : signal transduction knowledge environment·2001
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A genetic screen for modifiers of a kinase suppressor of Ras-dependent rough eye phenotype in Drosophila.

Genetics·2000
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Protein kinases and phosphatases in the Drosophila genome.

The Journal of cell biology·2000
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Identification of B-KSR1, a novel brain-specific isoform of KSR1 that functions in neuronal signaling.

Molecular and cellular biology·2000

Related Experiment Video

Updated: Jul 25, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

KSR: a MAPK scaffold of the Ras pathway?

D K Morrison1

  • 1Regulation of Cell Growth Laboratory, National Cancer Institute, Frederick Cancer Reseach and Development Center, Frederick, MD 21702, USA. morrisod@nciaxp.ncifcrf.gov

Journal of Cell Science
|April 20, 2001
PubMed
Summary

Kinase Suppressor of Ras (KSR) is not a kinase but a scaffold protein. It organizes the MAP kinase cascade, crucial for Ras-mediated signal transduction, despite its name suggesting kinase activity.

Area of Science:

  • Cellular signaling and signal transduction pathways.
  • Molecular biology and protein function.
  • Genetics and developmental biology.

Background:

  • Kinase Suppressor of Ras (KSR) was identified in genetic studies in Drosophila and C. elegans.
  • KSR mutations suppress activated Ras phenotypes, suggesting a role in the Ras pathway.
  • KSR's kinase-like features initially led to speculation of its enzymatic activity.

Purpose of the Study:

  • To investigate the functional role of Kinase Suppressor of Ras (KSR) in signal transduction.
  • To clarify whether KSR possesses kinase activity or functions through other mechanisms.
  • To understand KSR's interactions within the MAP kinase cascade.

Main Methods:

  • Genetic analysis in model organisms (Drosophila melanogaster, Caenorhabditis elegans).

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Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

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  • Biochemical studies to assess protein kinase properties.
  • Interaction studies with MAP kinase cascade components (Raf-1, MEK1/2, ERK1/2).

    • Main Results:

    • KSR lacks key properties of known functional protein kinases.
    • KSR interacts with multiple components of the MAP kinase cascade.
    • Evidence suggests KSR functions as a scaffold, not an enzyme.

    Conclusions:

    • KSR's name is misleading; it does not appear to function as a kinase.
    • KSR acts as a scaffolding protein, facilitating MAP kinase complex assembly.
    • This coordination is vital for Ras-mediated signal transduction.