ANGIOTENSIN-II TYPE-1 RECEPTOR MEDIATES CELL-PROLIFERATION VIA PROTEIN-TYROSINE KINASE AND VOLTAGE-DEPENDENT CALCIUM CHANNELS

Citation
Y. Ozawa et al., ANGIOTENSIN-II TYPE-1 RECEPTOR MEDIATES CELL-PROLIFERATION VIA PROTEIN-TYROSINE KINASE AND VOLTAGE-DEPENDENT CALCIUM CHANNELS, Biomedical research, 19(1), 1998, pp. 1-8
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
Journal title
ISSN journal
0388-6107
Volume
19
Issue
1
Year of publication
1998
Pages
1 - 8
Database
ISI
SICI code
0388-6107(1998)19:1<1:ATRMCV>2.0.ZU;2-Z
Abstract
Here we examined the signaling pathway mediated by angiotensin II (Ang II) type 1 receptor (AT(1)) leading to Ang II-induced proliferation o f PC 12 cells stably expressing the recombinant AT(1) receptor (PC12/r AT1). The cell number increased to 2.4-fold over the control 4 days af ter Ang II addition. Ang II-induced [H-3]thymidine incorporation was a ffected neither by pertussis toxin nor by calphostin C, a protein kina se C (PKC) inhibitor. In contrast, the Ang II effect was almost comple tely inhibited by the protein tyrosine kinase (PTK) inhibitor genistei n. In addition, tyrphostin AG1478, an epidermal growth factor (EGF) re ceptor-selective inhibitor, significantly inhibited Ang II-induced [H- 3]thymidine incorporation but had no effect on the basic fibroblast gr owth factor action. Nicardipine, an L-type Ca2+ channel blocker, also inhibited the Ang II function. Together, these data demonstrate that G i proteins and PKC are not involved in Ang II-induced cell proliferati on of PC12/rAT1 cells through the AT(1) receptor, and that Ca2+ influx through voltage-dependent Ca2+ channels and activation of PTK(s) are critical for this process. Furthermore, our data suggest that ligand-i ndependent activation of a receptor tyrosine kinase(s), called transac tivation, plays an important role in AT(1)-mediated cell proliferation through Gq proteins.