Schroder Wayne, Bushell Gillian, Sculley Tom
The Queensland Institute of Medical Research, 300 Herston Road, Brisbane 4029, Australia.
Cell Signal. 2005 Jun;17(6):761-7. doi: 10.1016/j.cellsig.2004.10.015. Epub 2004 Dec 15.
The orthologous proteins of the stress-activated protein kinase-interacting 1 (Sin1) family have been implicated in several different signal transduction pathways. In this study, we have investigated the function of the full-length human Sin1 protein and a C-terminally truncated isoform, Sin1alpha, which is produced by alternative splicing. Immunoblot analysis using an anti-Sin1 polyclonal antibody showed that full-length Sin1 and several smaller isoforms are widely expressed. Sin1 was demonstrated to bind to c-Jun N-terminal kinase (JNK) in vitro and in vivo, while no interaction with p38- or ERK1/2-family MAPKs was observed. The Sin1alpha isoform could also form a complex with JNK in vivo. Despite localizing in distinct compartments within the cell, both Sin1 and Sin1alpha co-localized with JNK, suggesting that the Sin1 proteins could recruit JNK. Over-expression of full-length Sin1 inhibited the activation of JNK by UV-C in DG75 cells, as well as basal JNK-activity in HEK293 cells. These data suggest that the human Sin1 proteins may act as scaffold molecules in the regulation of signaling by JNK.
应激激活蛋白激酶相互作用蛋白1（Sin1）家族的直系同源蛋白参与了多种不同的信号转导途径。在本研究中，我们研究了全长人Sin1蛋白和一种通过可变剪接产生的C末端截短异构体Sin1α的功能。使用抗Sin1多克隆抗体进行的免疫印迹分析表明，全长Sin1和几种较小的异构体广泛表达。在体外和体内，Sin1均被证明可与c-Jun氨基末端激酶（JNK）结合，而未观察到与p38或ERK1/2家族丝裂原活化蛋白激酶（MAPK）的相互作用。Sin1α异构体在体内也可与JNK形成复合物。尽管Sin1和Sin1α定位于细胞内不同的区室，但它们均与JNK共定位，这表明Sin1蛋白可募集JNK。全长Sin1的过表达抑制了DG75细胞中紫外线C（UV-C）诱导的JNK激活以及HEK293细胞中的基础JNK活性。这些数据表明，人Sin1蛋白可能在JNK信号调节中作为支架分子发挥作用。
