Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding
作者： Y. Diao , W. Liu , C. C. L. Wong , X. Wang , K. Lee
关键词:
摘要: Mitogen-activated protein kinase 6 (MKK6) is a member of the mitogen-activated (MAPK) (MAP2K) subfamily that specifically phosphorylates and activates p38 MAPKs. Based on both biochemical cellular assays, we found MKK6 was extremely sensitive to oxidation: It inactivated by oxidation its activity fully restored upon treatment with reducing agent. Detailed mechanistic studies showed cysteines 109 196, two six in MKK6, formed an intramolecular disulfide bond inhibiting ATP binding. This mechanism distinct from seen other redox-sensitive kinases. The involved formation are conserved all seven members MAP2K family. Consistently, confirmed MAP2Ks were also oxidation. Our work reveals class redox sensors.
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