EP2 and EP4 prostanoid receptor signaling

被引:363
作者
Regan, JW [1 ]
机构
[1] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA
关键词
G-protein coupled receptors; prostaglandins; PGE2; cAMP; cancer;
D O I
10.1016/j.lfs.2003.09.031
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The EP2 and EP4 prostanoid receptors are two of the four subtypes of receptors for prostaglandin E-2 (PGE(2)). They are in the family of G-protein coupled receptors and both receptors were initially characterized as coupling to Gs and increasing intracellular cAMP formation. Recently, however, we have shown that both receptors can stimulate T-cell factor (Tcf) mediated transcriptional activity. The EP2 receptor does this primarily through cAMP-dependent protein kinase (PKA), whereas the EP4 utilizes phosphatidylinositol 3-kinase (PI3K) as well as PKA. In addition, we have shown that the EP4 receptor, but not the EP2, can activate the extracellular signal-regulated kinases (ERKs) I and 2 by way of PI3K leading to the induction of early growth response factor-1 (EGR-1), a transcription factor traditionally associated with wound healing. This induction of EGR-1 expression has significant implications concerning the potential role of PGE(2) in cancer and inflammatory disorders. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:143 / 153
页数:11
相关论文
共 43 条
[41]  
WATABE A, 1993, J BIOL CHEM, V268, P20175
[42]   Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor [J].
Yang, L ;
Yamagata, N ;
Yadav, R ;
Brandon, S ;
Courtney, RL ;
Morrow, JD ;
Shyr, Y ;
Boothby, M ;
Joyce, S ;
Carbone, DP ;
Breyer, RM .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (05) :727-735
[43]   Stimulation of bone formation and prevention of bone loss by prostaglandin E EP4 receptor activation [J].
Yoshida, K ;
Oida, H ;
Kobayashi, T ;
Maruyama, T ;
Tanaka, M ;
Katayama, T ;
Yamaguchi, K ;
Segi, E ;
Tsuboyama, T ;
Matsushita, M ;
Ito, K ;
Ito, Y ;
Sugimoto, Y ;
Ushikubi, F ;
Ohuchida, S ;
Kondo, K ;
Nakamura, T ;
Narumiya, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (07) :4580-4585