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Mammalian phosphatidylinositol transfer proteins: emerging roles in signal transduction and vesicular traffic

Cockcroft, S; (1999) Mammalian phosphatidylinositol transfer proteins: emerging roles in signal transduction and vesicular traffic. CHEMISTRY AND PHYSICS OF LIPIDS , 98 (1-2) 23 - 33.

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Abstract

Phosphatidylinositol transfer proteins (PITP) are abundant cytosolic proteins found in all mammalian cells. Two cytosolic isoforms of 35 and 36 kDa (PITP alpha and PITP beta) have been identified which share 77% identity. These proteins are characterized by having a single phospholipid binding site which exhibits dual headgroup specificity. The preferred lipid that can occupy the site can be either phosphatidylinositol (PI) or phosphatidylcholine (PC). In addition, PITP beta can also bind sphingomyelin. A second characteristic of these proteins is the ability to transfer PI and PC (or SM) from one membrane compartment to another in vitro. The function of PITP in mammalian cells has been examined mainly using reconstitution studies utilizing semi-intact cells or cell-free systems. From such analyses, a requirement for PITP has been identified in phospholipase C-mediated phosphatidylinositol bisphosphate (PI(4,5)P-2) hydrolysis, in phosphoinositide 3-kinase catalyzed PIP3 generation, in regulated exocytosis, in the biogenesis of secretory granules and vesicles and in intra-golgi transport. Studies aimed at elucidating the mechanism of action of PITP in each of these seemingly disparate processes have yielded a singular theme: the activity of PITP stems from its ability to transfer PI from its site of synthesis to sites of cellular activity. This function was predicted from its in vitro characteristics. The second feature of PITP that was not predicted is the ability to stimulate the local synthesis of several phosphorylated forms of PI including PI(4)P, PI(4,5)P-2, PI(3)P, PI(3,4,5)P-3 by presenting PI to the lipid kinases involved in phosphoinositide synthesis. We conclude that PITP contributes in multiple aspects of cell biology ranging from signal transduction to membrane trafficking events where a central role for phosphoinositides is recognized either as a substrate or as an intact lipid signalling molecule. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

Type: Article
Title: Mammalian phosphatidylinositol transfer proteins: emerging roles in signal transduction and vesicular traffic
Location: SENDAI, JAPAN
Keywords: phosphatidylinositol, phospholipase C, exocytosis, vesicle formation, phosphoinositide 3-kinase, signal transduction, RETINAL-DEGENERATION-B, CONSTITUTIVE TRANSPORT VESICLES, PHOSPHOLIPID TRANSFER PROTEINS, PLECKSTRIN HOMOLOGY DOMAIN, ADP-RIBOSYLATION-FACTOR, PLASMA-MEMBRANE, GOLGI NETWORK, SECRETORY VESICLES, CA2+-ACTIVATED EXOCYTOSIS, PHOSPHOINOSITIDE BINDING
UCL classification: UCL > Provost and Vice Provost Offices
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/120428
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