| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 281, Issue 6, 3408-3417, February 10, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Pharmacology, Institute for Chemical Biology, and Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-6600
In mammalian cells, phospholipase D activity is tightly regulated by diverse cellular signals, including hormones, neurotransmitters, and growth factors. Multiple signaling pathways converge upon phospholipase D to modulate cellular actions, such as cell growth, shape, and secretion. We examined the kinetics of protein kinase C and G-protein regulation of mammalian phospholipase D1 (PLD1) in order to better understand interactions between PLD1 and its regulators. Activation by Arf-1, RhoA, Rac1, Cdc42, protein kinase C
, and phosphatidylinositol 4,5-bisphosphate displayed surface dilution kinetics, but these effectors modulated different kinetic parameters. PKC activation of PLD1 involves N- and C-terminal PLD domains. Rho GTPases were binding activators, enhancing the catalytic efficiency of a purified PLD1 catalytic domain via effects on Km. Arf-1, a catalytic activator, stimulated PLD1 by enhancing the catalytic constant, kcat. A kinetic description of PLD1 activation by multiple modulators reveals a mechanism for apparent synergy between activators. Synergy was observed only when PLD1 was simultaneously stimulated by a binding activator and a catalytic activator. Surprisingly, synergistic activation was steeply dependent on phosphatidylinositol 4,5-bisphosphate and phosphatidylcholine. Together, these findings suggest a role for PLD1 as a signaling node, in which integration of convergent signals occurs within discrete locales of the cellular membrane.
Received for publication, August 10, 2005 , and in revised form, December 6, 2005.
* This work was supported by National Institutes of Health Grant GM58516. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Ingram Professor of Cancer Research in Pharmacology. To whom correspondence should be addressed. Tel.: 615-936-3888; Fax: 615-936-6833; E-mail: alex.brown{at}vanderbilt.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Garcia, Y. Zheng, C. Zhao, A. Toschi, J. Fan, N. Shraibman, H. A. Brown, D. Bar-Sagi, D. A. Foster, and J. L. Arbiser Honokiol Suppresses Survival Signals Mediated by Ras-Dependent Phospholipase D Activity in Human Cancer Cells Clin. Cancer Res., July 1, 2008; 14(13): 4267 - 4274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Exton In Search of the Message J. Biol. Chem., May 30, 2008; 283(22): 14901 - 14909. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Kolsch, P. G. Charest, and R. A. Firtel The regulation of cell motility and chemotaxis by phospholipid signaling J. Cell Sci., March 1, 2008; 121(5): 551 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Holinstat, B. Voss, M. L. Bilodeau, and H. E. Hamm Protease-Activated Receptors Differentially Regulate Human Platelet Activation through a Phosphatidic Acid-Dependent Pathway Mol. Pharmacol., March 1, 2007; 71(3): 686 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Preininger, L. G. Henage, W. M. Oldham, E. J. Yoon, H. E. Hamm, and H. A. Brown Direct Modulation of Phospholipase D Activity by Gbeta{gamma} Mol. Pharmacol., July 1, 2006; 70(1): 311 - 318. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
