TY - JOUR
T1 - Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells
AU - Wang, Qin
AU - Liu, Min
AU - Kozasa, Tohru
AU - Rothstein, Jeffrey D.
AU - Sternweis, Paul C.
AU - Neubig, Richard R.
PY - 2004/7/9
Y1 - 2004/7/9
N2 - Thrombin and lysophosphatidic acid (LPA) receptors play important roles in vascular biology, development, and cancer. These receptors activate rho via G12/13 family heterotrimeric G proteins, which are known to directly activate three distinct rho guanine nucleotide exchange factors (rhoGEFs) that contain a regulator of G protein signaling (RGS) domain (RGS-rhoGEFs). However, it is not known which, if any, of these RGS-rhoGEFs (LARG (leukemia-associated rhoGEF), p115rhoGEF, or PDZrhoGEF) plays a role in G protein-coupled receptor-stimulated rho signaling. Using oligonucleotide small interfering RNAs that suppress specific RGS-rhoGEF expression, we show that thrombin receptor stimulation of rho is primarily mediated by LARG in HEK293T and PC-3 prostate cancer cell lines. In contrast, the LPA-stimulated rho response in PC-3 cells is dependent on PDZrhoGEF expression. Suppression of p115rhoGEF had no effect. Thus different rho-GEFs (LARG and PDZrhoGEF) mediate downstream rho signaling by the thrombin and LPA receptors.
AB - Thrombin and lysophosphatidic acid (LPA) receptors play important roles in vascular biology, development, and cancer. These receptors activate rho via G12/13 family heterotrimeric G proteins, which are known to directly activate three distinct rho guanine nucleotide exchange factors (rhoGEFs) that contain a regulator of G protein signaling (RGS) domain (RGS-rhoGEFs). However, it is not known which, if any, of these RGS-rhoGEFs (LARG (leukemia-associated rhoGEF), p115rhoGEF, or PDZrhoGEF) plays a role in G protein-coupled receptor-stimulated rho signaling. Using oligonucleotide small interfering RNAs that suppress specific RGS-rhoGEF expression, we show that thrombin receptor stimulation of rho is primarily mediated by LARG in HEK293T and PC-3 prostate cancer cell lines. In contrast, the LPA-stimulated rho response in PC-3 cells is dependent on PDZrhoGEF expression. Suppression of p115rhoGEF had no effect. Thus different rho-GEFs (LARG and PDZrhoGEF) mediate downstream rho signaling by the thrombin and LPA receptors.
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U2 - 10.1074/jbc.C400105200
DO - 10.1074/jbc.C400105200
M3 - Article
C2 - 15143072
AN - SCOPUS:3142730924
SN - 0021-9258
VL - 279
SP - 28831
EP - 28834
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 28
ER -