Yang S H, Yates P R, Whitmarsh A J, Davis R J, Sharrocks A D
Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, United Kingdom.
Mol Cell Biol. 1998 Feb;18(2):710-20. doi: 10.1128/MCB.18.2.710.
The phosphorylation of transcription factors by mitogen-activated protein kinases (MAP) is a pivotal event in the cellular response to the activation of MAP kinase signal transduction pathways. Mitogenic and stress stimuli activate different pathways and lead to the activation of distinct groups of target proteins. Elk-1 is targeted by three distinct MAP kinase pathways. In this study, we demonstrate that the MAP kinase ERK2 is targeted to Elk-1 by a domain which is distinct from, and located N-terminally to, its phosphoacceptor motifs. Targeting via this domain is essential for the efficient and rapid phosphorylation of Elk-1 in vitro and full and rapid activation in vivo. Specific residues involved in ERK targeting have been identified. Our data indicate that the targeting of different classes of MAP kinases to their nuclear substrates may be a common mechanism to increase the specificity and efficiency of this signal transduction pathway.
丝裂原活化蛋白激酶（MAP）介导的转录因子磷酸化是细胞对MAP激酶信号转导途径激活作出反应的关键事件。促有丝分裂和应激刺激激活不同的途径，并导致不同组别的靶蛋白激活。Elk-1受三种不同的MAP激酶途径作用。在本研究中，我们证明MAP激酶ERK2通过一个与其磷酸化接受基序不同且位于其N端的结构域作用于Elk-1。通过该结构域的作用对于体外Elk-1的高效快速磷酸化以及体内的完全快速激活至关重要。已鉴定出参与ERK作用的特定残基。我们的数据表明，不同类别的MAP激酶作用于其核底物可能是增加该信号转导途径特异性和效率的常见机制。
