Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells

Qin Wang, Min Liu, Tohru Kozasa, Jeffrey D. Rothstein, Paul C. Sternweis, Richard R. Neubig

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)28831-28834
Number of pages4
JournalJournal of Biological Chemistry
Issue number28
StatePublished - Jul 9 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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