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Updated: Jun 24, 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

Functional proteomics identifies targets of phosphorylation by B-Raf signaling in melanoma

William M Old1, John B Shabb, Stephane Houel

  • 1Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.

Molecular Cell
|April 14, 2009
PubMed

Insights

Oncogenic B-Raf mutations drive melanoma by altering signaling pathways. This study introduces a novel phosphoproteomics method to identify key phosphorylation events, revealing MINERVA/FAM129B

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Oncogenic mutations in B-Raf kinase activate MAP kinase signaling, driving cancer progression.
  • Understanding B-Raf's molecular control over cancer phenotypes is crucial for targeted therapies.

Purpose of the Study:

  • To develop and apply a novel phosphoprotein profiling method for B-Raf signaling analysis.
  • To identify key phosphorylation events regulated by oncogenic B-Raf in melanoma.

Main Methods:

  • Utilized negative ionization mass spectrometry for phosphopeptide detection.
  • Developed a phosphoproteomics strategy avoiding affinity enrichment and isotopic labeling.
  • Analyzed melanoma cells treated with an MKK1/2 inhibitor to identify B-Raf-regulated phosphorylation.

Main Results:

  • Identified 90 phosphorylation events regulated by oncogenic B-Raf signaling.
  • Discovered that regulated phosphoproteins include signaling effectors and cytoskeletal regulators.
  • Established the role of MINERVA/FAM129B and its MAP kinase-dependent phosphorylation in melanoma cell invasion.

Conclusions:

  • The novel phosphoproteomics method offers an efficient alternative for studying signaling pathways.
  • MINERVA/FAM129B is a novel B-Raf signaling target critical for melanoma cell invasion.
  • Targeting B-Raf-regulated phosphorylation presents a potential therapeutic strategy for melanoma.

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