Am J Physiol Cell Physiol Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol (February 23, 2005). doi:10.1152/ajpcell.00610.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/1/C2    most recent
00610.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yun, C. C.
Right arrow Articles by Shim, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yun, C. C.
Right arrow Articles by Shim, H.
Submitted on December 13, 2004
Accepted on February 15, 2005

The LPA2 receptor mediates mitogenic signals in human colon cancer cells

C. Chris Yun1, Hong Sun1*, Dongsheng Wang1, Raluca Rusovici1, Amanda Castleberry1, Randy A Hall1, and Hyunsuk Shim1

1 Medicine, Emory University, Atlanta, Ga, USA

* To whom correspondence should be addressed. E-mail: ccyun{at}emory.edu.

Lysophosphatidic acid (LPA) is a mediator of multiple cellular responses. LPA mediates its effects predominantly through the G protein-coupled receptors, LPA1, LPA2, and LPA3. In the present work, we studied LPA2-mediated signaling using human colon cancer cell lines, which predominantly express LPA2. LPA2 activated Akt and Erk1/2 in response to LPA. LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase C{beta}, U73122. LPA also induced interleukin-8 (IL-8) synthesis in the colon cancer cells by primarily activating LPA2 receptor. We also found that LPA2 interacts with Na+/H+ exchanger regulatory factor 2 (NHERF2). Activation of Akt and Erk1/2 was significantly attenuated by silencing of NHERF2 expression by RNA interference, suggesting a pivotal role of NHERF2 in LPA2-mediated signaling. We also found that expression of LPA2 was elevated, whereas expression of LPA1 down-regulated in several types of cancers, including ovarian and colon cancer. We conclude that LPA2 is the major LPA receptor in colon cancer cells and cellular signals by LPA2 are largely mediated through its ability to interact with NHERF2.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
T. T. Chiu, W. Y. Leung, M. P. Moyer, R. M. Strieter, and E. Rozengurt
Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 production in nontransformed human colonic epithelial cells through NF-{kappa}B
Am J Physiol Cell Physiol, February 1, 2007; 292(2): C767 - C777.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Murph, T. Tanaka, S. Liu, and G. B. Mills
Of Spiders and Crabs: The Emergence of Lysophospholipids and Their Metabolic Pathways as Targets for Therapy in Cancer.
Clin. Cancer Res., November 15, 2006; 12(22): 6598 - 6602.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Z. Lee, R. F. Swaby, Y. Liang, S. Yu, S. Liu, K. H. Lu, R. C. Bast Jr., G. B. Mills, and X. Fang
Lysophosphatidic Acid Is a Major Regulator of Growth-Regulated Oncogene {alpha} in Ovarian Cancer.
Cancer Res., March 1, 2006; 66(5): 2740 - 2748.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
C. Li, K. S. Dandridge, A. Di, K. L. Marrs, E. L. Harris, K. Roy, J. S. Jackson, N. V. Makarova, Y. Fujiwara, P. L. Farrar, et al.
Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions
J. Exp. Med., October 3, 2005; 202(7): 975 - 986.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.