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hKSR-2 inhibits MEKK3-activated MAP kinase and NF-kappaB pathways in inflammation.

Abstract：

:Kinase suppressor of ras (KSR) and MEKK3 (MAP kinase kinase kinase) are integral members of the MAP kinase pathway. We have recently identified a new isoform of the KSR family named human kinase suppressor of ras-2 (hKSR-2), and demonstrated that hKSR-2 negatively regulates Cot, a MAP3K family member which is important in inflammation and oncogenesis [P.L. Channavajhala, L. Wu, J.W. Cuozzo, J.P. Hall, W. Liu, L.L. Lin, Y. Zhang, J. Biol. Chem. 278 (2003) 47089-47097]. In this report, we provide evidence that hKSR-2 also regulates the activity of MEKK3 (another MAP3K family member) in HEK-293T cells. We demonstrate that hKSR-2 is a negative regulator of MEKK3-mediated activation of MAP kinase (specifically ERK and JNK) and NF-kappaB pathways, and concurrently inhibits MEKK3-mediated interleukin-8 production. We find that while hKSR-2 blocks MEKK3 activation, it has little to no effect on other members of the MAP3K family, including MEKK4, TAK1, and Ras-Raf, suggesting that its effects are selective.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Channavajhala PL,Rao VR,Spaulding V,Lin LL,Zhang YG

doi

10.1016/j.bbrc.2005.07.009

subject

Has Abstract

pub_date

2005-09-09 00:00:00

pages

1214-8

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(05)01468-3

journal_volume

334

pub_type

杂志文章

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