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Updated: Nov 3, 2025

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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RAB7A Regulates Vimentin Phosphorylation through AKT and PAK

Roberta Romano1, Matteo Calcagnile1, Azzurra Margiotta1

  • 1Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy.

Cancers
|June 2, 2021
PubMed

Insights

The small GTPase RAB7A influences cell migration by regulating kinases AKT and PAK1, impacting downstream effectors like beta-catenin and MMP2, suggesting a role in cancer progression.

Area of Science:

  • Cell Biology
  • Molecular Biology

Background:

  • RAB7A, a small GTPase, is known to regulate the late endocytic pathway.
  • RAB7A also influences cell migration via RAC1 and vimentin, controlling vimentin phosphorylation and assembly.

Purpose of the Study:

  • To investigate the interaction domains between RAB7A and vimentin.
  • To determine if RAB7A modulates the activity of kinases involved in vimentin phosphorylation.
  • To explore the downstream effects of RAB7A-mediated kinase regulation on cellular processes.

Main Methods:

  • Identification of vimentin domains interacting with RAB7A.
  • Assessing the impact of RAB7A expression modulation on kinase activity (AKT, PAK1).
  • Quantifying phosphorylation changes at specific vimentin sites (e.g., Serine 38).
  • Measuring expression levels of downstream effectors (beta-catenin, caspase 9, cofilin-1) and enzyme activity (MMP2).

Main Results:

  • RAB7A regulates the activity of AKT and PAK1 kinases.
  • RAB7A overexpression increases vimentin phosphorylation at Serine 38, mediated by AKT.
  • RAB7A modulation affects beta-catenin and caspase 9 expression, cofilin-1 levels, and MMP2 activity.

Conclusions:

  • RAB7A acts as a regulator of AKT and PAK1 kinases.
  • RAB7A influences key cellular processes through these kinases and their downstream effectors.
  • These findings suggest a potential role for RAB7A in various cancer hallmarks.
Keywords:
NF-kBRAC1beta-catenincell migrationcofilinintermediate filaments

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