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Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry

T S Lewis1, J B Hunt, L D Aveline

  • 1Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.

Molecular Cell
|February 13, 2001
PubMed

Insights

Functional proteomics identified 25 targets of the MKK/ERK cascade, revealing novel roles in nuclear transport, DNA repair, and cytoskeletal regulation. This study expands understanding of the mitogen-activated protein (MAP) kinase pathway effectors.

Area of Science:

  • Molecular Biology
  • Proteomics
  • Cell Signaling

Background:

  • Functional proteomics monitors cellular responses to signaling pathway activation, including protein modifications and expression.
  • The MKK/ERK cascade is a key signal transduction pathway with incompletely characterized downstream effectors.

Purpose of the Study:

  • To identify novel cellular targets regulated by the MKK/ERK cascade using functional proteomics.
  • To elucidate new roles of the MKK/ERK pathway in cellular processes.

Main Methods:

  • Selective activation and inhibition of MKK1/2.
  • Application of functional proteomics to analyze global molecular responses.
  • Mass spectrometry-based proteomics for target identification.

Main Results:

  • Twenty-five targets regulated by the MKK/ERK cascade were identified.
  • Only five of the identified targets were previously known MKK/ERK effectors.
  • Novel roles were suggested in nuclear transport, nucleotide excision repair, nucleosome assembly, membrane trafficking, and cytoskeletal regulation.

Conclusions:

  • Functional proteomics is a powerful discovery-based strategy for identifying signaling pathway targets.
  • This study revealed novel effectors and functions of the MKK/ERK signaling cascade.
  • The findings expand the known scope of MAP kinase pathway regulation in cellular processes.

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