Burgermeister Elke, Lanzendoerfer Martin, Scheuer Werner
Dept. of Biological Regulation, The Weizmann Institute of Science, I-76100 Rehovot, Israel.
J Biomol Struct Dyn. 2003 Apr;20(5):623-34. doi: 10.1080/07391102.2003.10506879.
Nuclear receptor (NR) agonists induce activation of mitogen-activated protein kinases (MAPK) through an yet unknown rapid non-genomic mechanism. Vice versa, NR are targets for phosphorylation by MAPK. By multiple alignment of the amino acid sequences and comparative analysis of the secondary and tertiary structures we identified four peptides in MAPK with similarity to bona fide protein-protein-interaction motifs in NR. In both molecule species, these motifs mediate selective docking to dimerization partners, coregulators or phosphoacceptors. We therefore propose that similar motifs may direct the site-specific association of NR with MAPK. Based on mutual allosteric interactions within a kinase-receptor complex, we discuss a novel principle how NR-agonists may regulate kinase activity and thus expression of hormone-dependent genes.
核受体（NR）激动剂通过一种尚未明确的快速非基因组机制诱导丝裂原活化蛋白激酶（MAPK）的激活。反之，NR是MAPK磷酸化的靶点。通过对氨基酸序列的多重比对以及对二级和三级结构的比较分析，我们在MAPK中鉴定出了四种与NR中真正的蛋白质-蛋白质相互作用基序相似的肽段。在这两种分子类型中，这些基序介导与二聚化伙伴、共调节因子或磷酸化受体的选择性对接。因此，我们提出相似的基序可能指导NR与MAPK的位点特异性结合。基于激酶-受体复合物内的相互变构相互作用，我们讨论了一种新的原理，即NR激动剂如何调节激酶活性，进而调节激素依赖性基因的表达。
