Phosphorylation of NF-κB1/p105 by oncoprotein kinase Tpl2:: Implications for a novel mechanism of Tpl2 regulation
Phosphorylation of NF-κB1/p105 by oncoprotein kinase Tpl2:: Implications for a novel mechanism of Tpl2 regulation
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DOI：
10.1016/j.bbamcr.2005.12.010
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发表时间：
2006-02-01
影响因子：
5.1
通讯作者：
Sun, SC
中科院分区：
文献类型：
--
作者：
Babu, GR;Jin, W;Sun, SC
肿瘤蛋白激酶Tp12在巨噬细胞被细菌成分脂多糖（LPS）激活的过程中起重要作用。在LPS刺激下，Tp12磷酸化下游激酶MEK1，导致ERK信号通路的激活。最近的研究表明，NF-kappa B1前体蛋白p105作为Tp12的抑制剂，并且lps刺激的Tp12激活需要p105降解。然而，p105如何抑制Tp12的信号功能尚不完全清楚。我们在这里证明p105不会抑制Tp12的内在激酶活性。当与p105配合时，Tp12保持催化活性并使用p105作为底物。然而，p105结合的Tp12无法磷酸化其生理靶标MEK1。这些发现表明p105作为Tp12的竞争性抑制剂，阻断其通过MEK1的通路。(c) 2005 Elsevier B.V.版权所有
The oncoprotein kinase Tp12 plays an essential role in macrophage activation by the bacterial component lipopolysaccharide (LPS). In response to LPS stimulation, Tp12 phosphorylates a downstream kinase, MEK1, leading to the activation of ERK signaling pathway. Recent studies demonstrate that the NF-kappa B1 precursor protein p105 functions as an inhibitor of Tp12 and that the LPS-stimulated Tp12 activation requires p105 degradation. However, how p105 inhibits the signaling function of Tp12 is not completely understood. We show here that p105 does not inhibit the intrinsic kinase activity of Tp12. When complexed with p105, Tp12 remains catalytically active and uses p105 as a substrate. However, the p105-bound Tp12 is unable to phosphorylate its physiological target, MEK1. These findings suggest that p105 functions as a competitive inhibitor of Tp12 that blocks its access by MEK1. (c) 2005 Elsevier B.V. All rights reserved.