Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation
Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation
复制标题
DOI：
10.1126/science.284.5412.309
复制
发表时间：
1999-04-09
期刊：
影响因子：
56.9
通讯作者：
Karin, M
中科院分区：
文献类型：
--
作者：
Delhase, M;Hayakawa, M;Karin, M
IκB[核因子κB（NF - κB）抑制剂]激酶（IKK）使IκB抑制蛋白磷酸化，导致其降解以及转录因子NF - κB的激活，NF - κB是炎症反应的主要激活因子。IKK由三个亚基组成——IKKα和IKKβ，它们是高度相似的蛋白激酶，以及IKKγ，一个调节亚基。在哺乳动物细胞中，IKKβ激活环上两个位点的磷酸化对于肿瘤坏死因子和白细胞介素 - 1激活IKK至关重要。然而，去除IKKα中相应的位点并不干扰IKK的激活。因此，IKKβ，而非IKKα，是促炎刺激的靶点。一旦被激活，IKKβ会在羧基末端的丝氨酸簇处发生自身磷酸化。这种磷酸化会降低IKK的活性，并可能防止炎症反应的过度激活。
I kappa B [inhibitor of nuclear factor kappa B (NF-kappa B)] kinase (IKK) phosphorylates I kappa B inhibitory proteins, causing their degradation and activation of transcription factor NF-KB, a master activator of inflammatory responses. IKK is composed of three subunits-IKK alpha and IKK beta, which are highly similar protein kinases, and IKK gamma, a regulatory subunit. In mammalian cells, phosphorylation of two sites at the activation Loop of IKK beta was essential for activation of IKK by tumor necrosis factor and interleukin-1. Elimination of equivalent sites in IKK alpha, however, did not interfere with IKK activation. Thus, IKK beta, not IKK alpha, is the target for proinflammatory stimuli. Once activated, IKK beta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response.