Phospholipase D (PLD) hydrolyses phosphatidylcholine into phosphatidic acid (PA) and choline. Our work aims to understand the properties of PLD1, and to identify downstream targets of PA. In one set of projects, we have focused on membrane-targeting mechanisms and have proposed a hierarchy of signals that allows PLD1 to localize to intracellular membranes. These signals involve a functional pleckstrin homology (PH) domain and its fatty acylation on two adjacent cysteine residues. A nearby Phox homology (PX) domain may modulate the function of the fatty acylated PH domain. This complex array of signals is probably necessitated by the targeting of PLD1 to multiple endocytic and secretory membranes under basal and signal-dependent conditions. In another set of projects, we have used chemically synthesized PA coupled to a solid support in order to identify proteins that interact with this phospholipid. Several proteins have emerged from this screen as potential targets. Some (e.g. ADP-ribosylation factor, coatomer β subunit) are involved in trafficking and their PA affinity can be understood in terms of their regulated cycling on and off membranes during rounds of transport. Others (sphingosine 1-phosphate kinase and PtdIns4P 5-kinase) are implicated in pathways that also involve PLD activation. Others still are novel proteins (brain-specific neurochondrin) whose affinity for PA may contribute to an understanding of their cellular function.
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February 2003
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Conference Article|
February 01 2003
Phospholipase D1 and potential targets of its hydrolysis product, phosphatidic acid
N.T. Ktistakis;
N.T. Ktistakis
1
Department of Signalling, Babraham Institute, Babraham, Cambridge CB2 4AT, U.K.
1To whom correspondence should be addressed (e-mail nicholas.ktistakis@bbsrc.ac.uk).
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C. Delon;
C. Delon
Department of Signalling, Babraham Institute, Babraham, Cambridge CB2 4AT, U.K.
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M. Manifava;
M. Manifava
Department of Signalling, Babraham Institute, Babraham, Cambridge CB2 4AT, U.K.
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E. Wood;
E. Wood
Department of Signalling, Babraham Institute, Babraham, Cambridge CB2 4AT, U.K.
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I. Ganley;
I. Ganley
Department of Signalling, Babraham Institute, Babraham, Cambridge CB2 4AT, U.K.
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J.M. Sugars
J.M. Sugars
Department of Signalling, Babraham Institute, Babraham, Cambridge CB2 4AT, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
Copyright 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (1): 94–97.
Citation
N.T. Ktistakis, C. Delon, M. Manifava, E. Wood, I. Ganley, J.M. Sugars; Phospholipase D1 and potential targets of its hydrolysis product, phosphatidic acid. Biochem Soc Trans 1 February 2003; 31 (1): 94–97. doi: https://doi.org/10.1042/bst0310094
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