Effects of angiotensin II on proximal tubular cells stably transfected with the c-mas oncogene.
Angiotensin II (ANG II) normally induces cellular hypertrophy in proximal tubular epithelium by engaging receptor systems that use a G-protein-signaling mechanism. The c-mas oncogene also encodes part of a superfamily of vasoactive peptide receptor-like moieties that couple to G proteins. To determine whether the stable expression of the c-mas gene might alter or modify the induction of cellular hypertrophy by ANG II in tubular epithelium, a rat c-mas cDNA was cloned into the pSV2 expression vector for use in cell transfection. Scatchard analysis of ANG II binding revealed no significant differences in ANG II receptor number or in the dissociation constant between pSV2mas-transfected or wild-type MCT cells, but rather an increase in the number of receptors not replaceable by known inhibitors. ANG II also induced proliferation in pSV2mas-transfected MCT cells that was not blocked by conventional inhibitors and increased intracellular levels of inositol trisphosphate. ANG II, furthermore, did not increase de novo protein synthesis in pSV2-transfected MCT cells and failed to lower their intracellular concentration of adenosine 3',5'-cyclic monophosphate, both expected parameters of cellular hypertrophy. Our findings demonstrate that expression of c-mas in tubular epithelium can modulate tubular cell phenotype toward proliferation rather than hypertrophy. This effect is likely mediated by a reshuffling of the heterogeneity of ANG II receptors on the cell surface, or perhaps by the emergence of a new ANG II receptor, followed by alterations in the process of signal transduction.
Wolf
G
G
Department of Medicine, University of Frankfurt, Federal Republic of Germany.
Neilson
E G
EG
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D014176:Protein Biosynthesis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011945:Receptors, Angiotensin / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D014162:Transfection
D015335:Molecular Probes; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011945:Receptors, Angiotensin; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP