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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2006.1
- 수록면
- 546 - 552 (7page)
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IκB kinase β (IKKβ) subunit of IKK complex is essential for the activation of NF-κB in response to various proinflammatory signals. Cys-179 in the activation loop of IKKβ is known to be the target site for IKK inhibitors such as cyclopentenone pros-taglandins, arsenite, and antirheumatic gold com-pounds. Here we show that a mutant IKKβ in which Cys-179 is substituted with alanine had decreased activity when it was exprTNF stimulation did not restore the activity. Phos-phorylation of activation loop serines (Ser-177 and Ser-181) which is required for IKKβ activation was reduced in the IKKβ (C179A) mutant. The activity of IKKβ (C179A) was partially recovered when its phosphorylation was enforced by coexpression with mitogen-activated protein kinase kinase kinases (MAPKKK) such as NF-κB inducing kinase (NIK) and MAPK/extracellular signal-regulated kinase kinase kinase 1(MEKK1) or when the serine residues were replaced with phospho-mimetic glutamate. The IKKβ (C179A) mutant was normal in dimer formation, while its activity abnormally responded to the change in the concentration of substrate Our results suggest that Cys-179 of IKKβ plays a critical role in enzyme activation by promoting phosphorylation of activation-loop serines and interaction with ATP.
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참고문헌 (23)
참고문헌 신청
/ 1996 / Active and inactive protein kinases structural basis for regulation 85 : 149 ~ 158
/ 1997 / IKK1 and IKK2 cytokine activated IB kinases essential for NFB activation 278 : 860 ~ 866
/ 1997 / Nuclear factor B a pivotal transcription factor in chronic inflammatory diseases 336 : 1066 ~ 1071
/ 1998 / Coordinate regulation of IB kinases by mitogen activated protein kinase kinase kinase 1and NF B inducing kinase 18 : 7336 ~ 7343
/ 1998 / Differential regulation of IB kinase alpha and beta by two upstream kinases NFB inducing kinase and mitogen activated protein kinase ERK kinase kinase1 95 : 3537 ~
/ 1997 / IKK1 and IKK2 cytokine activated IB kinases essential for NFB activation 278 : 860 ~ 866
/ 1997 / Nuclear factor B a pivotal transcription factor in chronic inflammatory diseases 336 : 1066 ~ 1071
/ 1998 / Coordinate regulation of IB kinases by mitogen activated protein kinase kinase kinase 1and NF B inducing kinase 18 : 7336 ~ 7343
/ 1998 / Differential regulation of IB kinase alpha and beta by two upstream kinases NFB inducing kinase and mitogen activated protein kinase ERK kinase kinase1 95 : 3537 ~
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