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MEKK2 regulates paxillin ubiquitylation and localization in MDA-MB 231 breast cancer cells

Magdalene Ameka1, Michael P Kahle1, Mathew Perez-Neut1

  • 1*Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, U.S.A.

The Biochemical Journal
|September 6, 2014
PubMed

Insights

Mitogen-activated protein kinase kinase kinase 2 (MEKK2) regulates breast tumor cell migration and metastasis. MEKK2 induces paxillin ubiquitylation, promoting its cytoplasmic redistribution from focal adhesions.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase kinase 2 (MEKK2) is an intracellular kinase known to regulate JNK signaling.
  • MEKK2 plays a role in tumor progression, as silencing it inhibits xenograft metastasis in invasive breast tumor cells.
  • Previous studies linked MEKK2 to focal adhesion complexes and tumor cell migration.

Purpose of the Study:

  • To investigate the function of MEKK2 within focal adhesions.
  • To elucidate the molecular mechanism by which MEKK2 influences tumor cell behavior.

Main Methods:

  • Investigated MEKK2 interaction with paxillin using biochemical assays.
  • Assessed the role of the paxillin LD1 motif and MEKK2 kinase activity in ubiquitylation.
  • Utilized cell-based assays to track paxillin localization and degradation.

Main Results:

  • MEKK2 physically associates with the LD1 motif of the focal adhesion protein paxillin.
  • MEKK2 induces paxillin ubiquitylation, dependent on the LD1 motif and MEKK2 kinase activity.
  • MEKK2 promotes paxillin redistribution from focal adhesions to the cytoplasm without causing degradation.

Conclusions:

  • MEKK2 functions in focal adhesions to regulate paxillin.
  • MEKK2 controls ubiquitylation-dependent paxillin redistribution, impacting breast tumor cell behavior.
  • This novel mechanism highlights MEKK2's role in tumor cell migration and metastasis.

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