Synergistic activation of SAPK1/JNK1 by two MAP kinase kinases in vitro
Synergistic activation of SAPK1/JNK1 by two MAP kinase kinases in vitro
复制标题
DOI：
10.1016/s0960-9822(98)00019-0
复制
发表时间：
1998-12-17
期刊：
影响因子：
9.2
通讯作者：
Cohen, P
中科院分区：
文献类型：
--
作者：
Lawler, S;Fleming, Y;Cohen, P
丝裂原活化蛋白激酶（MAPK）介导生长因子、细胞因子和应激刺激的许多细胞效应。它们的激活需要位于Thr-X-Tyr基序（其中X是任何氨基酸）中的苏氨酸和酪氨酸残基的磷酸化[1]。这种磷酸化是由MAPK激酶（MKK）催化的，它们都被认为是“双重特异性”酶，可以磷酸化Thr-X-Tyr基序的苏氨酸和酪氨酸残基[2]。（SAPK 1c，也称为JNK 1）[3]在体外被MKK 4（[4-6];也称为SKK 1和JNKK 1）和MKK 7（[7-9];也称为SKK 4和JNKK 2）协同激活。我们发现，MKK 4有一个优先的酪氨酸残基，和MKK 7的苏氨酸残基，在Thr-X-Tyr基序。这些观察结果表明，SAPK 1c在体内的完全激活有时可能需要两种不同的MKK的磷酸化，提供了整合不同细胞外信号的作用的潜力。他们还提出了其他MAPK家族成员可能被两个或更多个MKK激活的可能性，并且一些MKK可能未被检测到，因为它们仅磷酸化酪氨酸残基，因此除非苏氨酸首先被另一个MKK磷酸化，否则不会诱导任何激活。
Mitogen-activated protein kinases (MAPKs) mediate many of the cellular effects of growth factors, cytokines and stress stimuli. Their activation requires the phosphorylation of a threonine and a tyrosine residue located in a Thr-X-Tyr motif (where X is any amino acid) [1]. This phosphorylation is catalysed by MAPK kinases (MKKs), which are all thought to be 'dual specificity' enzymes that phosphorylate both the threonine and the tyrosine residue of the Thr-X-Tyr motif [2], Here, we report that the MAPK family member known as stress activated protein kinase-1c (SAPK1c, also known as JNK1) [3] is activated synergistically in vitro by MKK4 ([4-6]; also called SKK1 and JNKK1) and MKK7 ([7-9]; also called SKK4 and JNKK2). We found that MKK4 had a preference for the tyrosine residue, and MKK7 for the threonine residue, within the Thr-X-Tyr motif. These observations suggest that the full activation of SAPK1c in vivo may sometimes require phosphorylation by two different MKKs, providing the potential for integrating the effects of different extracellular signals. They also raise the possibility that other MAPK family members may be activated by two or more MKKs and that some MKKs may have gone undetected because they phosphorylate the tyrosine residue only, and therefore do not induce any activation unless the threonine has first been phosphorylated by another MKK.