PIP kinases from the cell membrane to the nucleus

Abstract

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a membrane bound lipid molecule with capabilities to affect a wide array of signaling pathways to regulate very different cellular processes. PIP2 is used as a precursor to generate the second messengers PIP3, DAG and IP3, indispensable molecules for signaling events generated by membrane receptors. However, PIP2 can also directly regulate a vast array of proteins and is emerging as a crucial messenger with the potential to distinctly modulate biological processes critical for both normal and pathogenic cell physiology. PIP2 directly associates with effector proteins via unique phosphoinositide binding domains, altering their localization and/or enzymatic activity. The spatial and temporal generation of PIP2 synthesized by the phosphatidylinositol phosphate kinases (PIPKs) tightly regulates the activation of receptor signaling pathways, endocytosis and vesicle trafficking, cell polarity, focal adhesion dynamics, actin assembly and 3’ mRNA processing. Here we discuss our current understanding of PIPKs in the regulation of cellular processes from the plasma membrane to the nucleus.