PIPKI? regulates ?-catenin transcriptional activity downstream of growth factor receptor signaling.

ABSTRACT: Increased ?-catenin transcriptional activity downstream of the Wnt/Wingless signaling pathway has been observed in many human tumors, most notably colorectal carcinomas. However, ?-catenin activation is also observed in many human malignancies with no observable Wnt activity. Wnt-independent pathways that activate ?-catenin remain undefined, yet have the potential to play a significant role during tumorigenesis. Here, we report that phosphotidylinositol phosphate kinase I? (PIPKI?), an enzyme that generates phosphoinositide messengers in vivo, directly associates with ?-catenin and increases ?-catenin activity downstream of growth factor stimulation. PIPKI? expression and kinase activity enhance ?-catenin phosphorylation on residues that promote nuclear importation and transcriptional activity. Lastly, we show that ?-catenin is required for PIPKI?-dependent increased cell proliferation. These results reveal a novel mechanism in which PIPKI? expression and catalytic activity enhance ?-catenin nuclear translocation and expression of its target genes to promote tumorigenic phenotypes.

SUBMITTER: Schramp M 

PROVIDER: S-EPMC3066690 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature