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Biochim Biophys Acta. 2015 Jun;1851(6):711-23. doi: 10.1016/j.bbalip.2015.01.009. Epub 2015 Jan 21.

PIP kinases define PI4,5P₂signaling specificity by association with effectors.

Author information

1
Cellular and Molecular Biology Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
2
Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
3
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.

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.

KEYWORDS:

Interaction; PI4,5P(2); PI4,5P(2) effector; PIP kinase; Phosphoinositide; Phosphoinositide kinase

PMID:
25617736
PMCID:
PMC4380618
DOI:
10.1016/j.bbalip.2015.01.009
[Indexed for MEDLINE]
Free PMC Article

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