title: PIP kinases define PI4,5P₂signaling specificity by association with effectors.
abstract: Phosphatidylinositol 4,5-bisphosphate (PI4,5P₂) is an essential lipid messenger with roles in all eukaryotes and most aspects of human physiology. By controlling the targeting and activity of its effectors, PI4,5P₂modulates processes, such as cell migration, vesicular trafficking, cellular morphogenesis, signaling and gene expression. In cells, PI4,5P₂has a much higher concentration than other phosphoinositide species and its total content is largely unchanged in response to extracellular stimuli. The discovery of a vast array of PI4,5P₂ binding proteins is consistent with data showing that the majority of cellular PI4,5P₂is sequestered. This supports a mechanism where PI4,5P₂functions as a localized and highly specific messenger. Further support of this mechanism comes from the de novo synthesis of PI4,5P₂which is often linked with PIP kinase interaction with PI4,5P₂effectors and is a mechanism to define specificity of PI4,5P₂signaling. The association of PI4,5P₂-generating enzymes with PI4,5P₂effectors regulate effector function both temporally and spatially in cells. In this review, the PI4,5P₂effectors whose functions are tightly regulated by associations with PI4,5P₂-generating enzymes will be discussed. This article is part of a Special Issue entitled Phosphoinositides.
authors.affiliation: Cellular and Molecular Biology Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Suyong
authors.initials: S
authors.lastname: Choi
authors.affiliation: Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Narendra
authors.initials: N
authors.lastname: Thapa
authors.affiliation: Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tan
authors.affiliation: Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hedman
authors.affiliation: Cellular and Molecular Biology Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA; Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA. Electronic address: raanders@wisc.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism; D016608:Talin / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D018260:Gelsolin; D008024:Ligands; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; C107953:RAC1 protein, human; D058305:Sorting Nexins; D016608:Talin; D017853:Phosphotransferases (Alcohol Group Acceptor); D019061:src-Family Kinases; D002154:Calpain; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins
keywords: Interaction; PI4,5P(2); PI4,5P(2) effector; PIP kinase; Phosphoinositide; Phosphoinositide kinase