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Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks.

Clayton, EL; Minogue, S; Waugh, MG; (2013) Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks. Prog Lipid Res , 52 (3) 294 - 304. 10.1016/j.plipres.2013.04.002. Green open access

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Abstract

The four mammalian phosphatidylinositol 4-kinases modulate inter-organelle lipid trafficking, phosphoinositide signalling and intracellular vesicle trafficking. In addition to catalytic domains required for the synthesis of PI4P, the phosphatidylinositol 4-kinases also contain isoform-specific structural motifs that mediate interactions with proteins such as AP-3 and the E3 ubiquitin ligase Itch, and such structural differences determine isoform-specific roles in membrane trafficking. Moreover, different permutations of phosphatidylinositol 4-kinase isozymes may be required for a single cellular function such as occurs during distinct stages of GPCR signalling and in Golgi to lysosome trafficking. Phosphatidylinositol 4-kinases have recently been implicated in human disease. Emerging paradigms include increased phosphatidylinositol 4-kinase expression in some cancers, impaired functioning associated with neurological pathologies, the subversion of PI4P trafficking functions in bacterial infection and the activation of lipid kinase activity in viral disease. We discuss how the diverse and sometimes overlapping functions of the phosphatidylinositol 4-kinases present challenges for the design of isoform-specific inhibitors in a therapeutic context.

Type: Article
Title: Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.plipres.2013.04.002
Publisher version: http://dx.doi.org/10.1016/j.plipres.2013.04.002
Language: English
Additional information: �© 2013 Elsevier Ltd. All rights reserved. This work is licensed under a Creative Commons Attribution 3.0 Unported License. PMCID: PMC3989048
Keywords: 1-Phosphatidylinositol 4-Kinase, Animals, Bacterial Infections, Glycosphingolipids, Humans, Isoenzymes, Neoplasms, Nervous System Diseases, Phosphatidylinositol Phosphates, Receptors, G-Protein-Coupled, Signal Transduction, Sphingomyelins, Virus Diseases
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Education
URI: https://discovery.ucl.ac.uk/id/eprint/1392859
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