Brenner B, Koppenhoefer U, Weinstock C, Linderkamp O, Lang F, Gulbins E
Department of Pediatrics, University of Heidelberg, INF 150, 69120 Heidelberg, Germany.
J Biol Chem. 1997 Aug 29;272(35):22173-81. doi: 10.1074/jbc.272.35.22173.
In the present study, we show that Fas receptor ligation or cellular treatment with synthetic C6-ceramide results in activation or phosphorylation, respectively, of the small G-protein Rac1, Jun N-terminal kinase (JNK)/p38 kinases (p38-K), and the transcription factor GADD153. A signaling cascade from the Fas receptor via ceramide, Ras, Rac1, and JNK/p38-K to GADD153 is demonstrated employing transfection of transdominant inhibitory N17Ras, N17Rac1, c-Jun, or treatment with a specific p38-K inhibitor. The critical function of this signaling cascade is indicated by prevention of Fas- or C6-ceramide-induced apoptosis after inhibition of Ras, Rac1, or JNK/p38-K.
在本研究中，我们发现Fas受体连接或用合成的C6-神经酰胺进行细胞处理分别导致小G蛋白Rac1、Jun N端激酶（JNK）/p38激酶（p38-K）和转录因子GADD153的激活或磷酸化。通过转染显性抑制性N17Ras、N17Rac1、c-Jun或用特定的p38-K抑制剂处理，证明了从Fas受体经神经酰胺、Ras、Rac1和JNK/p38-K到GADD153的信号级联反应。抑制Ras、Rac1或JNK/p38-K后，Fas或C6-神经酰胺诱导的细胞凋亡受到抑制，这表明了该信号级联反应的关键功能。
