A role for p21(ras) in the angiotensin II AT(2) receptor transduction pathway

We have previously shown that the activation of the AT, receptor of Ang II induced neurite outgrowth in NG108-15 cells. We also found that stimulation of NG108-15 cells with Ang II induced a rapid decrease in GTP-bound p21(ra s). In order to investigate the possible role of p21(ras) in Ang II-induced neuronal differentiation, we have established NG108-15 sublines which indu cibly express a dominant inhibitory form of p21(ras) (p21N17Ras). We observ ed that IPTG-induced expression of p21N17Ras in these NG108-15 sublines ind uced the same morphological changes as does Ang II in control untransfected cells. Immunofluorescence labeling of beta-tubulin showed that expression of p21N17Ras induced neurite outgrowth and elongation. These observations w ere supported by Western blot analysis of the level of polymerized tubulin. These results strongly support the hypothesis that AT(2) receptor-induced neuronal differentiation in NG108-15 cells is mediated by the inhibition of p21(ras).