Signals from the AT2 (angiotensin type 2) receptor of angiotensin II inhibit p21ras and activate MAPK (mitogen-activated protein kinase) to induce morphological neuronal differentiation in NG108-15 cells

被引:94
作者
Gendron, L
Laflamme, L
Rivard, N
Asselin, C
Payet, MD
Gallo-Payet, N [1 ]
机构
[1] Univ Sherbrooke, Fac Med, Serv Endocrinol, Sherbrooke, PQ J1H 5N4, Canada
[2] Univ Sherbrooke, Fac Med, Dept Anat & Cell Biol, Sherbrooke, PQ J1H 5N4, Canada
[3] Univ Sherbrooke, Fac Med, Dept Physiol & Biophys, Sherbrooke, PQ J1H 5N4, Canada
关键词
D O I
10.1210/me.13.9.1615
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In a previous study, we had shown that activation of the AT(2) (angiotensin type 2) receptor of angiotensin II (Ang II) induced morphological differentiation of the neuronal cell line NG108-15. In the present study, we investigated the nature of the possible intracellular mediators involved in the AT(2) effect. We found that stimulation of AT(2) receptors in NG108-15 cells resulted in time-dependent modulation of tyrosine phosphorylation of a number of cytoplasmic proteins. Stimulation of NG108-15 cells with Ang II induced a decrease in GTP-bound p21(ras) but a sustained increase in the activity of p42(mapk) and p44(mapk) as well as neurite outgrowth. Similarly, neurite elongation, increased polymerized tubulin levels, and increased mitogen-activated protein kinase (MAPK) activity were also observed in a stably transfected NG108-15 cell line expressing the dominant-negative mutant of p21(ras), RasN17. These results support the observation that inhibition of p21(ras) did not impair the effect of Ang II on its ability to stimulate MARK activity. While 10 mu M of the MEK inhibitor, PD98059, only moderately affected elongation, 50 mu M PD98059 completely blocked the Ang II- and the RasN17-mediated induction of neurite outgrowth, These results demonstrate that some of the events associated with the AT(2) receptor-induced neuronal morphological differentiation of NG108-15 cells not only include inhibition of p21(ras) but an increase in MARK activity as well, which is essential for neurite outgrowth.
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页码:1615 / 1626
页数:12
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