JCB logo
R&D Systems
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 6 June 2005. doi:10.1083/jcb.200407123
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 5, 801-811
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bektas, M.
Right arrow Articles by Spiegel, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bektas, M.
Right arrow Articles by Spiegel, S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 A novel acylglycerol kinase that produces lysophosphatidic acid modulates cross talk with EGFR in prostate cancer cells

Meryem Bektas1, Shawn G. Payne1, Hong Liu1, Sravan Goparaju1, Sheldon Milstien2, and Sarah Spiegel1

1 Department of Biochemistry and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298
2 Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, MD 20892

Correspondence to Sarah Spiegel: sspiegel{at}vcu.edu

The bioactive phospholipids, lysophosphatidic acid (LPA) and phosphatidic acid (PA), regulate pivotal processes related to the pathogenesis of cancer. Here, we report characterization of a novel lipid kinase, designated acylglycerol kinase (AGK), that phosphorylates monoacylglycerol and diacylglycerol to form LPA and PA, respectively. Confocal microscopy and subcellular fractionation suggest that AGK is localized to the mitochondria. AGK expression was up-regulated in prostate cancers compared with normal prostate tissues from the same patient. Expression of AGK in PC-3 prostate cancer cells markedly increased formation and secretion of LPA. This increase resulted in concomitant transactivation of the EGF receptor and sustained activation of extracellular signal related kinase (ERK) 1/2, culminating in enhanced cell proliferation. AGK expression also increased migratory responses. Conversely, down-regulating expression of endogenous AGK inhibited EGF- but not LPA-induced ERK1/2 activation and progression through the S phase of the cell cycle. Hence, AGK can amplify EGF signaling pathways and may play an important role in the pathophysiology of prostate cancer.

M. Bektas and S.G. Payne contributed equally to this paper.

Abbreviations used in this paper: AGK, acylglycerol kinase; DAG, 1,2-dioleoyl-sn-glycerol; DAGK, DAG kinase; ERK, extracellular signal related kinase; GPCR, G protein–coupled receptor; LPA, lysophosphatidic acid; MAGK, monoacylglycerol kinase; MOG, 1-oleoyl-2-sn-glycerol; PA, phosphatidic acid; PPAR{gamma}, peroxisome proliferator-activated receptor-{gamma}; PTX, pertussis toxin; S1P, sphingosine-1-phosphate; siRNA, small interfering RNA; SphK, sphingosine kinase.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents