Maher Pamela
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, CA 92037, USA.
Oncogene. 2002 Mar 27;21(13):1978-88. doi: 10.1038/sj.onc.1205268.
Treatment of fibroblasts with the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA), specifically inhibits fibroblast growth factor-2 (FGF-2) induced proliferation. TPA treatment has little or no effect on FGF receptor activation but specifically inhibits the activation of p38 MAPK but not other downstream signaling pathways implicated in cell proliferation. p38 MAPK was recently shown to be required for the FGF-2-stimulated proliferation of fibroblasts. The effect of TPA on both p38 MAPK activation and cell proliferation can be reversed by treatment with the PKC inhibitor Go6983. The TPA-mediated inhibition of p38 MAPK activation requires phosphatase activity and is at least partially mediated by ERKs since it is reduced by treatment with the MEK inhibitor PD98059. In contrast, the FGF-2-stimulated differentiation of PC12 cells, which express the same FGF receptor as Swiss 3T3 fibroblasts, is not affected by TPA treatment, consistent with a lack of involvement of p38 MAPK activity in this process. These data indicate that the effects of TPA treatment on cellular function are not only cell type but also stimulus specific and are dependent upon the distinct pathways activated downstream of each stimulus.
用佛波酯12 - O -十四酰佛波醇13 - 乙酸酯（TPA）处理成纤维细胞，可特异性抑制成纤维细胞生长因子2（FGF - 2）诱导的增殖。TPA处理对FGF受体激活几乎没有影响，但能特异性抑制p38丝裂原活化蛋白激酶（p38 MAPK）的激活，而不影响其他与细胞增殖相关的下游信号通路。最近研究表明，p38 MAPK是FGF - 2刺激成纤维细胞增殖所必需的。用蛋白激酶C（PKC）抑制剂Go6983处理可逆转TPA对p38 MAPK激活和细胞增殖的影响。TPA介导的对p38 MAPK激活的抑制作用需要磷酸酶活性，并且至少部分由细胞外信号调节激酶（ERK）介导，因为用MEK抑制剂PD98059处理可降低这种抑制作用。相比之下，TPA处理不影响PC12细胞（其表达与瑞士3T3成纤维细胞相同的FGF受体）的FGF - 2刺激的分化，这与p38 MAPK活性在该过程中未参与一致。这些数据表明，TPA处理对细胞功能的影响不仅具有细胞类型特异性，还具有刺激特异性，并且取决于每种刺激下游激活的不同信号通路。
