A dominant negative TAK1 inhibits cellular fibrotic responses induced by TGF-beta.

Abstract:

:Transforming growth factor-beta (TGF-beta) is crucially virulent in the progression of fibrotic disorders. TAK1 (TGF-beta activated kinase 1) is one of the mitogen-activated kinase kinase kinase (MAPKKK) that is involved in TGF-beta signal transduction. To elucidate the importance of TAK1 in TGF-beta-induced fibrotic marker expression, we investigated whether dominant negative TAK1 could suppress TGF-beta signaling. Based on the finding that TAB1 (TAK1 binding protein 1) binding to TAK1 is required for TAK1 activation, a minimal portion of TAK1 lacking kinase activity that binds to TAB1 was designed as a TAK1 dominant negative inhibitor (TAK1-DN). The effect of TAK1-DN was assessed in the cells that respond to TGF-beta stimulation and that lead to the increase in production of extracellular matrix (ECM) proteins. TAK1-DN, indeed, decreased the ECM protein production, indicating that TAK1-DN retains the ability to intercept the TGF-beta signaling effectively.

authors

Ono K,Ohtomo T,Ninomiya-Tsuji J,Tsuchiya M

doi

10.1016/s0006-291x(03)01207-5

subject

Has Abstract

pub_date

2003-07-25 00:00:00

pages

332-7

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006291X03012075

journal_volume

307

pub_type

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