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A signalling cascade involving PKC, Src and Cdc42 regulates podosome assembly in cultured endothelial cells in

Florence Tatin1, Christine Varon, Elisabeth Génot

  • 1Institut Européen de Chimie-Biologie, 2 rue Robert Escarpit, 33600 Pessac, France.

Journal of Cell Science
|February 2, 2006
PubMed

Insights

Protein kinase C (PKC) and Src signaling pathways regulate podosome assembly in endothelial cells. These dynamic structures are involved in matrix degradation during vascular remodeling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Podosomes are dynamic actin-rich structures involved in cell adhesion and matrix degradation.
  • The molecular regulators of podosome assembly in endothelial cells are not fully understood.

Purpose of the Study:

  • To investigate the roles of Src, Cdc42, RhoA, and protein kinase C (PKC) in podosome formation and function in endothelial cells.
  • To elucidate the signaling cascade leading to podosome assembly.

Main Methods:

  • Ectopic expression of constitutively active mutants.
  • Treatment with phorbol-12-myristate-13-acetate (PMA).
  • Pharmacological inhibition and siRNA knockdown of specific signaling molecules.
  • In vitro matrix degradation assays.

Main Results:

  • Src, Cdc42, and RhoA are involved in podosome assembly, with Src and Cdc42 being key regulators.
  • PKCalpha and PKCdelta are necessary for podosome assembly, with PKCalpha mimicking PMA effects.
  • A linear cascade involving PKC, Src, and Cdc42 regulates podosome formation.
  • PMA-induced podosomes exhibit proteolytic activity via MT1-MMP and MMP2.

Conclusions:

  • PKC signaling initiates podosome assembly in endothelial cells, followed by Src and Cdc42 activation.
  • Endothelial podosomes contribute to subendothelial matrix degradation, potentially playing a role in pathophysiological processes like vascular remodeling.

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