p21-activated kinase interacts with Wnt signaling to regulate tissue polarity and gene expression

Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15853-8. doi: 10.1073/pnas.1120795109. Epub 2012 Sep 10.

Abstract

Wnt signaling is mediated by three classes of receptors, Frizzled, Ryk, and Ror. In Caenorhabditis elegans, Wnt signaling regulates the anterior/posterior polarity of the P7.p vulval lineage, and mutations in lin-17/Frizzled cause loss or reversal of P7.p lineage polarity. We found that pak-1/Pak (p21-activated kinase), along with putative activators of Pak, nck-1/Nck, and ced-10/Rac, regulates P7.p polarity. Mutations in these genes suppress the polarity defect of lin-17 mutants. Furthermore, mutations in pak-1, nck-1, and ced-10 cause constitutive dauer formation at 27 °C, a phenotype also observed in egl-20/Wnt and cam-1/Ror mutants. In HEK293T cells, Pak1 can antagonize canonical Wnt signaling. Moreover, overexpression of Ror2 leads to phosphorylation of Pak1. Together, these results indicate that Pak interacts with Wnt signaling to regulate tissue polarity and gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Gene Expression Regulation, Developmental / physiology*
  • HEK293 Cells
  • Humans
  • L Cells
  • Mice
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Wnt Signaling Pathway / physiology*
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Nck protein
  • Oncogene Proteins
  • PAK1 protein, human
  • Pak1 protein, mouse
  • p21-Activated Kinases