RRC ID 46347
Author Goh KY, Ng NW, Hagen T, Inoue T.
Title p21-activated kinase interacts with Wnt signaling to regulate tissue polarity and gene expression.
Journal Proc Natl Acad Sci U S A
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.
Volume 109(39)
Pages 15853-8
Published 2012-9-25
DOI 10.1073/pnas.1120795109
PII 1120795109
PMID 23019370
PMC PMC3465426
MeSH 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*
IF 9.412
Times Cited 5
C.elegans tm403