Camarillo I G, Rillema J A
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Proc Soc Exp Biol Med. 1997 Oct;216(1):98-103. doi: 10.3181/00379727-216-44162.
The p21ras protein has been shown to be active in many growth factor signaling systems, including that of prolactin (PRL). In our studies, the main objective was to examine further the involvement of ras in prolactin-stimulated mitogenic and metabolic processes. We used the farnesylation inhibitor lovastatin to block effectively ras-dependent signaling in Nb2 cells, a pre-T lymphoma cell line, and mammary gland explants derived from 12- to 14-day pregnant mice. Lovastatin completely inhibited PRL-induced Nb2 cell mitogenesis at 1 micron. In the mammary gland, lovastatin at 0.1 micron inhibited the PRL stimulation of lipid and lactose synthesis; at 2 microns, lovastatin abolished the PRL stimulation of casein production. When p21ras was immunoprecipitated from lovastatin (25 microns)-treated Nb2 cells and mammary gland explants, the unfarnesylated (inactive) form of ras was shown to be redistributed from the cell membrane to the cytosolic compartment of the cell. This suggests that the anchoring of ras to the cell membrane is essential for its action in prolactin signal transduction. Thus, in addition to the well-known active participation of ras in mitogenic growth factor signaling, the presence of functional ras also appears necessary for the PRL stimulation of specific metabolic processes involved in lactation.
p21ras蛋白已被证实在包括催乳素（PRL）信号系统在内的多种生长因子信号系统中具有活性。在我们的研究中，主要目的是进一步研究ras在催乳素刺激的有丝分裂和代谢过程中的作用。我们使用法尼基化抑制剂洛伐他汀有效阻断Nb2细胞（一种前T淋巴瘤细胞系）和来自12至14天孕鼠的乳腺外植体中依赖ras的信号传导。洛伐他汀在1微摩尔浓度时完全抑制PRL诱导的Nb2细胞有丝分裂。在乳腺中，0.1微摩尔浓度的洛伐他汀抑制PRL对脂质和乳糖合成的刺激；在2微摩尔浓度时，洛伐他汀消除PRL对酪蛋白产生的刺激。当从用洛伐他汀（25微摩尔）处理的Nb2细胞和乳腺外植体中免疫沉淀p21ras时，未法尼基化（无活性）形式的ras被证明从细胞膜重新分布到细胞的胞质区室。这表明ras锚定在细胞膜上对其在催乳素信号转导中的作用至关重要。因此，除了ras在有丝分裂生长因子信号传导中众所周知的积极参与外，功能性ras的存在对于PRL刺激泌乳中涉及的特定代谢过程似乎也是必要的。
