Stimulation of the WNT pathway controls the activity of PIP5KB in a FZD- and DVL-dependent manner (Pan et al, 2008; Bilic et al, 2007; Cong et al, 2004; Qin et al, 2009). Activation of PIP5KB results in the formation of PI(4,5)P2 at the plasma membrane, which is required through an unclear mechanism for the phosphorylation of LRP6 at serine 1490, LRP6 aggregation into 'signalosomes' and LRP6 phosphorylation at threonine 1479. These events are required for the recruitment of AXIN to the plasma membrane (Pan et al, 2008; Qin et al, 2009).
DVL1 and 3 have been shown to co-immunoprecipitate with PIP5KB in HEK293 cells. This interaction is mediated by the N-terminal half of the kinase and the PDZ and DIX domain of DVL and recruits PIPK5B to the receptor complex. The interaction of DVL and PIP5KB is required for the WNT3A-dependent phosphorylation of LRP6 at serine 1490 and threonine 1479, as well as and the subsequent formation of the signalosome and recruitment of AXIN (Pan et al, 2008).
At the plasma membrane, phosphatidylinositol-4-phosphate 5-kinase type-1 alpha (PIP5K1A) and beta (PIP5K1B) phosphorylate phosphatidylinositol 3-phosphate (PI3P) to phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) (Tolias et al. 1998).
At the plasma membrane, phosphatidylinositol-4-phosphate 5-kinase type-1 alpha (PIP5K1A) and beta (PIP5K1B) phosphorylate phosphatidylinositol (PI) to produce phosphatidylinositol 5-phosphate (PI5P) (Tolias et al. 1998).
At the plasma membrane, phosphatidylinositol-4-phosphate 5-kinase type-1 alpha (PIP5K1A), beta (PIP5K1B), and gamma (PIP5K1C) phosphorylate phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) to produce phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). This is a minor reaction, however, and its physiological role is uncertain.
The following lists the above proteins with their corresponding literature references: PIP5K1A (Zhang et al. 1997, Tolias et al. 1998), PIP5K1B (Zhang et al. 1997, Tolias et al. 1998), and PIP5K1C (Wenk et al. 2001, Di Paolo et al. 2002, Krauss et al. 2003).
At the plasma membrane, phosphatidylinositol-4-phosphate 5-kinase type-1 alpha (PIP5K1A), beta (PIP5K1B), and gamma (PIP5K1C) phosphorylate phosphatidylinositol 4-phosphate (PI4P) to produce phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2).
The following lists the above proteins with their corresponding literature references: PIP5K1A (Halstead et al. 2006, Zhang et al. 1997), PIP5K1B (Zhang et al. 1997), and PIP5K1C (Di Paolo et al. 2002).
This reaction is of particular interest because its regulation by small GTPases of the RHO and ARF families, not yet annotated here, ties the process of phosphatidylinositol phosphate biosynthesis to regulation of the actin cytoskeleton and vesicular trafficking, and hence to diverse aspects of cell motility and signalling (Oude Weernink et al. 2004, 2007).
At the plasma membrane, phosphatidylinositol-5-phosphate 4-kinase type-2 alpha (PIP4K2A) and beta (PIP4K2B) homodimers and heterodimers (Clarke et al. 2010), along with phosphatidylinositol-4-phosphate 5-kinase type-1 alpha (PIP5K1A), beta (PIP5K1B), and gamma (PIP5K1C) phosphorylate phosphatidylinositol 3-phosphate (PI3P) to phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2).
The following lists the above proteins with their corresponding literature references: PIP4K2A (Zhang et al. 1997, Rameh et al. 1997, Clarke et al. 2008), PIP4K2B (Zhang et al. 1997, Rameh et al. 1997), PIP5K1A (Zhang et al. 1997, Tolias et al. 1998), PIP5K1B (Zhang et al. 1997, Tolias et al. 1998), and PIP5K1C (Wenk et al. 2001, Di Paolo et al. 2002).