Goedert M, Cuenda A, Craxton M, Jakes R, Cohen P
MRC Laboratory of Molecular Biology, Cambridge, UK.
EMBO J. 1997 Jun 16;16(12):3563-71. doi: 10.1093/emboj/16.12.3563.
A cDNA was cloned that encodes human stress-activated protein kinase-4 (SAPK4), a novel MAP kinase family member whose amino acid sequence is approximately 60% identical to that of the other three SAP kinases which contain a TGY motif in their activation domain. The mRNA encoding SAPK4 was found to be widely distributed in human tissues. When expressed in KB cells, SAPK4 was activated in response to cellular stresses and pro-inflammatory cytokines, in a manner similar to other SAPKs. SAPK4 was activated in vitro by SKK3 (also called MKK6) or when co-transfected with SKK3 into COS cells. SKK3 was the only activator of SAPK4 that was induced when KB cells were exposed to a cellular stress or stimulated with interleukin-1. These findings indicate that SKK3 mediates the activation of SAPK4. The substrate specificity of SAPK4 in vitro was similar to that of SAPK3. Both enzymes phosphorylated the transcription factors ATF2, Elk-1 and SAP-1 at similar rates, but were far less effective than SAPK2a (also called RK/p38) or SAPK2b (also called p38beta) in activating MAPKAP kinase-2 and MAPKAP kinase-3. Unlike SAPK1 (also called JNK), SAPK3 and SAPK4 did not phosphorylate the activation domain of c-Jun. Unlike SAPK2a and SAPK2b, SAPK4 and SAPK3 were not inhibited by the drugs SB 203580 and SB 202190. Our results suggest that cellular functions previously attributed to SAPK1 and/or SAPK2 may be mediated by SAPK3 or SAPK4.
克隆了一个编码人应激激活蛋白激酶4（SAPK4）的cDNA，它是丝裂原活化蛋白激酶（MAP激酶）家族的一个新成员，其氨基酸序列与其他三个在激活结构域中含有TGY基序的SAP激酶的氨基酸序列大约60%相同。发现编码SAPK4的mRNA在人体组织中广泛分布。当在KB细胞中表达时，SAPK4会响应细胞应激和促炎细胞因子而被激活，其方式与其他SAP激酶相似。SAPK4在体外被SKK3（也称为MKK6）激活，或者当与SKK3共转染到COS细胞中时被激活。SKK3是KB细胞受到细胞应激或用白细胞介素-1刺激时诱导产生的SAPK4的唯一激活剂。这些发现表明SKK3介导了SAPK4的激活。SAPK4在体外的底物特异性与SAPK3相似。这两种酶以相似的速率磷酸化转录因子ATF2、Elk-1和SAP-1，但在激活MAPKAP激酶-2和MAPKAP激酶-3方面远不如SAPK2a（也称为RK/p38）或SAPK2b（也称为p38β）有效。与SAPK1（也称为JNK）不同，SAPK3和SAPK4不磷酸化c-Jun的激活结构域。与SAPK2a和SAPK2b不同，SAPK4和SAPK3不受药物SB 203580和SB 202190的抑制。我们的结果表明，以前归因于SAPK1和/或SAPK2的细胞功能可能由SAPK3或SAPK4介导。
