Activation of FP prostanoid receptor isoforms leads to Rho-mediated changes in cell morphology and in the cell cytoskeleton

Citation
Kl. Pierce et al., Activation of FP prostanoid receptor isoforms leads to Rho-mediated changes in cell morphology and in the cell cytoskeleton, J BIOL CHEM, 274(50), 1999, pp. 35944-35949
Citations number
23
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
50
Year of publication
1999
Pages
35944 - 35949
Database
ISI
SICI code
0021-9258(199912)274:50<35944:AOFPRI>2.0.ZU;2-6
Abstract
Prostaglandin F-2 alpha (PGF(2 alpha)) exerts its biological effects by bin ding to and activating FP prostanoid receptors. These receptors, which incl ude two isoforms, the FPA and FPB, have been cloned from a number of specie s and are members of the superfamily of G-protein-coupled receptors. Previo us studies have shown that the activation of FP receptors leads to phosphat idylinositol hydrolysis, intracellular calcium release, and activation of p rotein kinase C. Here, we demonstrate that PGF(2 alpha) treatment of 293-EB NA (Epstein-Barr nuclear antigen) cells that have been stably transfected w ith either the FPA or FPB receptor isoforms leads to changes in cell morpho logy and in the cell cytoskeleton. Specifically, cells treated with PGF(2 a lpha) show retraction of filopodia and become rounded, and actin stress fib ers are formed. Pretreatment of the cells with bisindolylmaleimide I, a pro tein kinase C inhibitor, has no effect on the PGF(2 alpha)-induced changes in cell morphology, although it does block the effects of phorbol myristate acetate on cell morphology. On the other hand, the PGF(2 alpha)-induced ch anges in cell morphology and formation of actin stress fibers can be blocke d by pretreatment of the cells with C3 exoenzyme, a specific inhibitor of t he small G-protein, Rho. Consistent with FP receptor induced formation of a ctin stress fibers and focal adhesions, FPA receptor activation also leads to rapid (within two minutes) tyrosine phosphorylation of p125 focal adhesi on kinase (FAK) which can be blocked by pretreating the cells with C3 exoen zyme. Taken together, these results suggest that the FP receptor isoforms a re coupled to at least two second messenger pathways, one pathway associate d with protein kinase C activation, and the other with activation of Rho.