Hipk proteins dually regulate Wnt/Wingless signal transduction.

Fly (2012-05-29)
Esther M Verheyen, Sharan Swarup, Wendy Lee
ABSTRACT

The Wnt/Wingless (Wg) pathway is an evolutionarily conserved signaling system that is used reiteratively, both spatially and temporally, to control the development of multicellular animals. The stability of cytoplasmic β-catenin/Armadillo, the transcriptional effector of the pathway, is controlled by sequential N-terminal phosphorylation and ubiquitination that targets it for proteasome-mediated degradation. Orthologous members of the Homeodomain-interacting protein kinase family from Drosophila to vertebrates have been implicated in the regulation of Wnt/Wingless signaling. In Drosophila, as a consequence of Hipk activity, cells accumulate stabilized Armadillo that directs the expression of Wg-specific target genes. Hipk promotes the stabilization of Armadillo by inhibiting its ubiquitination (and hence subsequent degradation) by the SCF(Slimb) E3 ubiquitin ligase complex. Vertebrate Hipk2 impedes β-catenin ubiquitination to promote its stability and the Wnt signal in a mechanism that is functionally conserved. Moreover, we describe here that Hipk proteins have a role independent of their effect on β-catenin/Armadillo stability to enhance Wnt/Wingless signaling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Protein Kinase A from bovine heart, ≥0.4 units/μg protein, lyophilized powder
Sigma-Aldrich
Protein Kinase Cζ isozyme human, ≥75% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous solution
Sigma-Aldrich
Protein kinase CβII isozyme human, >85% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous glycerol solution
Sigma-Aldrich
Protein Kinase Cδ isozyme human, >95% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous glycerol solution
Sigma-Aldrich
Protein kinase Cγ isozyme human, >95% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous glycerol solution
Sigma-Aldrich
Protein Kinase CβI isozyme human, ≥95% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous glycerol solution