Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding

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	Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding
	Diao, YR ; Liu, W ; Wong, CCL ; Wang, X ; Lee, K ; Cheung, PY ; Pan, LF ; Xu, T ; Han, JH ; Yates, JR ; Zhang, MJ ; Wu, ZG ; Han JH(韩家淮)
刊名	http://dx.doi.org/10.1073/pnas.1007225107
	2010-12-07
关键词	TYROSINE-PHOSPHATASE 1B MAP KINASE HYDROGEN-PEROXIDE CYSTEINE OXIDATION REDOX REGULATION STRESS JNK MECHANISMS DISCOVERY PATHWAYS
英文摘要	Hong Kong Research Grant Council [663308, HKUST1/06C]; University Grants Council [AoE/B-15/01]; Mitogen-activated protein kinase kinase 6 (MKK6) is a member of the mitogen-activated protein kinase (MAPK) kinase (MAP2K) sub-family that specifically phosphorylates and activates the p38 MAPKs. Based on both biochemical and cellular assays, we found that MKK6 was extremely sensitive to oxidation: It was inactivated by oxidation and its kinase activity was fully restored upon treatment with a reducing agent. Detailed mechanistic studies showed that cysteines 109 and 196, two of the six cysteines in MKK6, formed an intramolecular disulfide bond upon oxidation that inactivated MKK6 by inhibiting its ATP binding. This mechanism is distinct from that seen in other redox-sensitive kinases. The two cysteines involved in intramolecular disulfide formation are conserved in all seven members of the MAP2K family. Consistently, we confirmed that other MAP2Ks were also sensitive to oxidation. Our work reveals that MKK6 and other MAP2Ks are a distinct class of cellular redox sensors.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65896]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Diao, YR,Liu, W,Wong, CCL,et al. Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding[J]. http://dx.doi.org/10.1073/pnas.1007225107,2010.
APA	Diao, YR.,Liu, W.,Wong, CCL.,Wang, X.,Lee, K.,...&韩家淮.(2010).Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding.http://dx.doi.org/10.1073/pnas.1007225107.
MLA	Diao, YR,et al."Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding".http://dx.doi.org/10.1073/pnas.1007225107 (2010).