Griffiths M R, Black E J, Culbert A A, Dickens M, Shaw P E, Gillespie D A, Tavaré J M
Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Biochem J. 1998 Oct 1;335 ( Pt 1)(Pt 1):19-26. doi: 10.1042/bj3350019.
The activator protein-1 (AP-1) transcriptional complex is made up of members of the Fos (c-Fos, FosB, Fra1, Fra2) and Jun (c-Jun, JunB, JunD) families and is stimulated by insulin in several cell types. The mechanism by which insulin activates this complex is not well understood but it is dependent on the activation of the Erk1 and Erk2 isoforms of mitogen-activated protein kinases. In the current study we show that the AP-1 complex isolated from insulin-stimulated cells contained c-Fos, Fra1, c-Jun and JunB. The activation of the AP-1 complex by insulin was accompanied by (i) a transient increase in c-fos expression, and the transactivation of the ternary complex factors Elk1 and Sap1a, in an Erk1/Erk2-dependent fashion; (ii) a substantial increase in the expression of Fra1 protein and mRNA, which was preceded by a transient decrease in its electrophoretic mobility upon SDS/PAGE, indicative of phosphorylation; and (iii) a sustained increase in c-jun expression without increasing c-Jun phosphorylation on serines 63 and 73 or activation of the stress-activated kinase JNK/SAPK. In conclusion, insulin appears to stimulate the activity of the AP-1 complex primarily through a change in the abundance of the components of this complex, although there may be an additional role for Fra1 phosphorylation.
激活蛋白-1（AP-1）转录复合体由Fos家族（c-Fos、FosB、Fra1、Fra2）和Jun家族（c-Jun、JunB、JunD）的成员组成，在多种细胞类型中受胰岛素刺激。胰岛素激活该复合体的机制尚不完全清楚，但它依赖于丝裂原活化蛋白激酶的Erk1和Erk2亚型的激活。在本研究中，我们发现从胰岛素刺激的细胞中分离出的AP-1复合体包含c-Fos、Fra1、c-Jun和JunB。胰岛素对AP-1复合体的激活伴随着：（i）c-fos表达的短暂增加，以及三元复合因子Elk1和Sap1a以Erk1/Erk2依赖的方式发生反式激活；（ii）Fra1蛋白和mRNA的表达大幅增加，在此之前其在SDS/PAGE上的电泳迁移率短暂下降，表明发生了磷酸化；（iii）c-jun表达持续增加，而丝氨酸63和73位的c-Jun磷酸化没有增加，应激激活激酶JNK/SAPK也未被激活。总之，胰岛素似乎主要通过改变该复合体组分的丰度来刺激AP-1复合体的活性，尽管Fra1磷酸化可能还有额外作用。
