title: PIP kinases from the cell membrane to the nucleus.
abstract: Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is a membrane bound lipid molecule with capabilities to affect a wide array of signaling pathways to regulate very different cellular processes. PIP(2) is used as a precursor to generate the second messengers PIP(3), DAG and IP(3), indispensable molecules for signaling events generated by membrane receptors. However, PIP(2) 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. PIP(2) directly associates with effector proteins via unique phosphoinositide binding domains, altering their localization and/or enzymatic activity. The spatial and temporal generation of PIP(2) 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.
authors.affiliation: Department of Pharmacology, School of Medicine and Public Health, 3710 Medical Sciences Center, University of Wisconsin Medical School, 1300 University Ave., 53706, Madison, WI, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Schramp
authors.forename: Andrew
authors.initials: A
authors.lastname: Hedman
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tan
authors.forename: Richard
authors.initials: R
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001692:Biological Transport; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D016764:Cell Polarity; D004075:Diglycerides / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000201:enzymology*; D005786:Gene Expression Regulation; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015290:Second Messenger Systems
chemical_list: D004075:Diglycerides; D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D017853:Phosphotransferases (Alcohol Group Acceptor)