Nguyen Quang, Lee Clement M, Le Anh, Reddy E Premkumar
Fels Institute for Cancer Research and Molecular Biology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
J Biol Chem. 2005 Aug 26;280(34):30185-91. doi: 10.1074/jbc.M505499200. Epub 2005 Jun 29.
Scaffolding proteins exist in eukaryotes to properly assemble signaling proteins into specific multimeric functional complexes. JLP is a novel leucine zipper protein belonging to a family of scaffolding proteins that assemble JNK signaling modules. JLP is a proline-rich protein that contains two leucine zipper domains and a highly conserved C-terminal domain. We have identified kinesin light chain 1 (KLC1) as a binding partner for the second leucine zipper domain of JLP using yeast two-hybrid screening. The interaction domain of KLC1 was mapped to its tetratripeptide repeat, which contains a novel leucine zipper-like domain that is crucial for the interaction with JLP. Mutations of Leu-280, Leu-287, Val-294, and Leu-301 within this domain of KLC1 disrupted its ability to associate with JLP. Immunofluorescence studies showed that JLP and KLC1 co-localized in the cytoplasm and that the localization of JLP was dependent on its second leucine zipper. Ectopic expression of a dominant negative form of KLC1 resulted in the mislocalization of endogenous JLP. Moreover, the association between JLP and KLC1 occurred in vivo and was important in the formation of ternary complex with JNK1. These results identify a novel protein-protein interaction between KLC1 and JLP that involves leucine zipper-like domains and support the role of motor proteins in the spatial regulation of signaling modules.
支架蛋白存在于真核生物中,可将信号蛋白正确组装成特定的多聚体功能复合物。JLP是一种新型亮氨酸拉链蛋白,属于组装JNK信号模块的支架蛋白家族。JLP是一种富含脯氨酸的蛋白,包含两个亮氨酸拉链结构域和一个高度保守的C末端结构域。我们通过酵母双杂交筛选鉴定出驱动蛋白轻链1(KLC1)是JLP第二个亮氨酸拉链结构域的结合伴侣。KLC1的相互作用结构域被定位到其四肽重复序列,该序列包含一个对与JLP相互作用至关重要的新型亮氨酸拉链样结构域。KLC1该结构域内Leu-280、Leu-287、Val-294和Leu-301的突变破坏了其与JLP结合的能力。免疫荧光研究表明,JLP和KLC1在细胞质中共定位,且JLP的定位依赖于其第二个亮氨酸拉链。KLC1显性负性形式的异位表达导致内源性JLP的定位错误。此外,JLP和KLC1之间的结合发生在体内,并且在与JNK1形成三元复合物中起重要作用。这些结果确定了KLC1和JLP之间一种涉及亮氨酸拉链样结构域的新型蛋白质-蛋白质相互作用,并支持了运动蛋白在信号模块空间调节中的作用。