Portier M, Combes T, Gully D, Maffrand J P, Casellas P
Sanofi Recherche, Montpellier, France.
FEBS Lett. 1998 Jul 31;432(1-2):88-93. doi: 10.1016/s0014-5793(98)00749-2.
Stimulation of neurotensin (NT) type 1 receptors (NT1-R) in transfected CHO cells is followed by the activation of mitogen-activated protein kinases and the expression of the early response gene krox24. By making point mutations and internal deletions in the krox24 promoter, we show that proximal serum responsive elements (SRE) are involved in transcriptional activation by NT. In addition, we show that the related early response gene c-fos and the Ets protein Elk-1 are also induced by NT. The involvement of NT1-R in NT-mediated activation of krox24, c-fos and Elk-1 was demonstrated by the preventing effect of the specific antagonists SR 48692 and SR 142948. Finally, we show that the activation of krox24 and Elk-1 on the one hand, and that of c-fos on the other hand, result from independent transduction pathways since the former are pertussis toxin-sensitive whereas the latter is insensitive to pertussis toxin.
在转染的CHO细胞中，神经降压素（NT）1型受体（NT1-R）受到刺激后，丝裂原活化蛋白激酶会被激活，早期反应基因krox24会表达。通过对krox24启动子进行点突变和内部缺失，我们发现近端血清反应元件（SRE）参与了NT介导的转录激活。此外，我们还表明相关的早期反应基因c-fos和Ets蛋白Elk-1也会被NT诱导。特异性拮抗剂SR 48692和SR 142948的阻断作用证明了NT1-R参与了NT介导的krox24、c-fos和Elk-1的激活。最后，我们表明，一方面krox24和Elk-1的激活，另一方面c-fos的激活，是由独立的转导途径导致的，因为前者对百日咳毒素敏感，而后者对百日咳毒素不敏感。
