Yang S H, Whitmarsh A J, Davis R J, Sharrocks A D
Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK.
EMBO J. 1998 Mar 16;17(6):1740-9. doi: 10.1093/emboj/17.6.1740.
The activation of MAP kinase (MAPK) signal transduction pathways results in the phosphorylation of transcription factors by the terminal kinases in these cascades. Different pathways are activated by mitogenic and stress stimuli, which lead to the activation of distinct groups of target proteins. The ETS-domain transcription factor Elk-1 is a substrate for three distinct classes of MAPKs. Elk-1 contains a targeting domain, the D-domain, which is distinct from the phosphoacceptor motifs and is required for efficient phosphorylation and activation by the ERK MAPKs. In this study, we demonstrate that members of the JNK subfamily of MAPKs are also targeted to Elk-1 by this domain. Targeting via this domain is essential for the efficient and rapid phosphorylation and activation of Elk-1 both in vitro and in vivo. The ERK and JNK MAPKs use overlapping yet distinct determinants in the D-domain for targeting to Elk-1. In contrast, members of the p38 subfamily of MAPKs are not targeted to Elk-1 via this domain. Our data therefore demonstrate that different classes of MAPKs exhibit differential requirements for targeting to Elk-1.
丝裂原活化蛋白激酶（MAPK）信号转导通路的激活会导致这些级联反应中的终端激酶使转录因子发生磷酸化。不同的通路由促有丝分裂和应激刺激激活，这会导致不同组别的靶蛋白被激活。ETS结构域转录因子Elk-1是三类不同MAPK的底物。Elk-1包含一个靶向结构域，即D结构域，它与磷酸化受体基序不同，是ERK MAPK进行有效磷酸化和激活所必需的。在本研究中，我们证明MAPK的JNK亚家族成员也通过该结构域靶向Elk-1。通过该结构域进行靶向对于Elk-1在体外和体内的有效且快速磷酸化及激活至关重要。ERK和JNK MAPK在D结构域中使用重叠但不同的决定簇来靶向Elk-1。相比之下，p38亚家族的MAPK成员不会通过该结构域靶向Elk-1。因此，我们的数据表明不同类别的MAPK对靶向Elk-1表现出不同的要求。
