Differential role for PAK1 and PAK4 during the invadopodia lifecycle

Small GTPases. 2019 Jul;10(4):289-295. doi: 10.1080/21541248.2017.1295830. Epub 2017 Mar 17.

Abstract

PAK1 and PAK4 are members of the p-21 activated kinase family of serine/threonine kinases. PAK1 has previously been implicated in both the formation and disassembly of invasive cell protrusions, termed invadopodia. We recently reported a novel role for PAK4 during invadopodia maturation and confirmed a specific role for PAK1 in invadopodia formation; findings we will review here. Moreover, we found that PAK4 induction of maturation is delivered via interaction with the RhoA regulator PDZ-RhoGEF. We can now reveal that loss of PAK4 expression leads to changes in invadopodia dynamics. Ultimately we propose that PAK4 but not PAK1 is a key mediator of RhoA activity and provide further evidence that modulation of PAK4 expression levels leads to changes in RhoA activity.

Keywords: PAK; RhoA; invadopodia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Neoplasm Invasiveness
  • Podosomes / metabolism*
  • Rho Guanine Nucleotide Exchange Factors / metabolism
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • ARHGEF11 protein, human
  • Rho Guanine Nucleotide Exchange Factors
  • RHOA protein, human
  • PAK4 protein, human
  • PAK1 protein, human
  • p21-Activated Kinases
  • rhoA GTP-Binding Protein