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TRAF-dependent association of protein kinase Tpl2/COT1 (MAP3K8) with CD40.

Abstract：

:Signaling by TNF-family receptor CD40 involves TRAF-family adaptor proteins, leading to activation of protein kinases that induce NFkappaB-family transcription factors. We report here that mitogen activated protein kinase kinase kinase-8 (MAP3K8), Tpl2/COT1, is recruited to the CD40 complex via a mechanism dependent on TRAF-binding sites in CD40. Tpl2/COT1 was shown to participate in CD40 signaling based on the ability of a catalytically inactive mutant to suppress CD40-mediated IkappaB kinase activation and induction of NFkappaB-responsive promoters, without affecting signaling by TNF. Tpl2 (-/-) fibroblasts were also deficient in CD40 but not TNF signaling, further supporting a unique role for Tpl2 in CD40 signaling. Experiments using dominant-negative Tpl2 suggest this kinase functions distal to TRAFs but proximal to the TAK1/TAB1 signaling complex, within the IKK/NFkappaB activation pathway. These results indicate a distinction between TNF Receptor family members CD40 and TNFR1 in their utilization of MAP3Ks, and demonstrate TRAF-dependence of Tpl2 association with the CD40 receptor complex.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Chan H,Reed JC

doi

10.1016/j.bbrc.2004.12.155

subject

Has Abstract

pub_date

2005-03-04 00:00:00

pages

198-205

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(04)02987-0

journal_volume

328

pub_type

杂志文章

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