Cell Biology

Wnt Receptor Signaling

Sci. Signal.  09 Sep 2008:
Vol. 1, Issue 36, pp. ec319
DOI: 10.1126/scisignal.136ec319

Wnt glycoproteins act as important signaling molecules in a range of processes from development to cancer. Pan et al. describe a missing link in the mechanism by which Wnt binding to its receptors initiates biochemical signaling within cells. They identified phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI) in a screen for components required for Wnt signaling in human cells. After activation, the Wnt receptor LRP6 becomes phosphorylated on serine and threonine residues, and PIP5KI was required for this event. The Wnt signaling component disheveled, a scaffold protein, interacted with PIP5KI, and disheveled and the Wnt receptor protein frizzled were required for Wnt-dependent formation of phosphatidylinositol 4,5-bisphosphate [PtdIns (4,5)P2]. Accumulation of PtdIns (4,5)P2 appeared to be necessary for the aggregation of LRP6 and its consequent phosphorylation.

W. Pan, S.-C. Choi, H. Wang, Y. Qin, L. Volpicelli-Daley, L. Swan, L. Lucast, C. Khoo, X. Zhang, L. Li, C. S. Abrams, S. Y. Sokol, D. Wu , Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science 321, 1350-1353 (2008). [Abstract] [Full Text]