Scholars@Duke publication: Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding.

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

Publication , Journal Article

Diao, Y; Liu, W; Wong, CCL; Wang, X; Lee, K; Cheung, P-Y; Pan, L; Xu, T; Han, J; Yates, JR; Zhang, M; Wu, Z

Published in: Proc Natl Acad Sci U S A

December 7, 2010

Mitogen-activated protein kinase kinase 6 (MKK6) is a member of the mitogen-activated protein kinase (MAPK) kinase (MAP2K) subfamily 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.

Duke Scholars

Author Yarui Diao Cell Biology

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.1007225107

EISSN

1091-6490

Publication Date

December 7, 2010

Volume

107

Issue

Start / End Page

20974 / 20979

Location

United States

Related Subject Headings

Protein Binding
Oxidation-Reduction
Mitogen-Activated Protein Kinase Kinases
MAP Kinase Kinase 6
Humans
Disulfides
Cysteine
Adenosine Triphosphate

Citation

APA

Chicago

ICMJE

MLA

NLM

Diao, Y., Liu, W., Wong, C. C. L., Wang, X., Lee, K., Cheung, P.-Y., … Wu, Z. (2010). Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding. Proc Natl Acad Sci U S A, 107(49), 20974–20979. https://doi.org/10.1073/pnas.1007225107

Diao, Yarui, Wei Liu, Catherine C. L. Wong, Xi Wang, Kaman Lee, Po-yan Cheung, Lifeng Pan, et al. “Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding.” Proc Natl Acad Sci U S A 107, no. 49 (December 7, 2010): 20974–79. https://doi.org/10.1073/pnas.1007225107.

Diao Y, Liu W, Wong CCL, Wang X, Lee K, Cheung P-Y, et al. Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding. Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):20974–9.

Diao, Yarui, et al. “Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding.” Proc Natl Acad Sci U S A, vol. 107, no. 49, Dec. 2010, pp. 20974–79. Pubmed, doi:10.1073/pnas.1007225107.

Diao Y, Liu W, Wong CCL, Wang X, Lee K, Cheung P-Y, Pan L, Xu T, Han J, Yates JR, Zhang M, Wu Z. Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding. Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):20974–20979.

Published In

Proc Natl Acad Sci U S A

DOI

10.1073/pnas.1007225107

EISSN

1091-6490

Publication Date

December 7, 2010

Volume

107

Issue

Start / End Page

20974 / 20979

Location

United States

Related Subject Headings

Protein Binding
Oxidation-Reduction
Mitogen-Activated Protein Kinase Kinases
MAP Kinase Kinase 6
Humans
Disulfides
Cysteine
Adenosine Triphosphate