Transforming growth factor beta1 signaling via interaction with cell surface Hyal-2 and recruitment of WWOX/WOX1.

ABSTRACT: Transforming growth factor beta (TGF-beta) initiates multiple signal pathways and activates many downstream kinases. Here, we determined that TGF-beta1 bound cell surface hyaluronidase Hyal-2 on microvilli in type II TGF-beta receptor-deficient HCT116 cells, as determined by immunoelectron microscopy. This binding resulted in recruitment of proapoptotic WOX1 (also named WWOX or FOR) and formation of Hyal-2.WOX1 complexes for relocation to the nuclei. TGF-beta1 strengthened the binding of the catalytic domain of Hyal-2 with the N-terminal Tyr-33-phosphorylated WW domain of WOX1, as determined by time lapse fluorescence resonance energy transfer analysis in live cells, co-immunoprecipitation, and yeast two-hybrid domain/domain mapping. In promoter activation assay, ectopic WOX1 or Hyal-2 alo

SUBMITTER: Hsu LJ 

PROVIDER: S-EPMC2708898 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature