A dominant negative TAK1 inhibits cellular fibrotic responses induced by TGF-β
K Ono, T Ohtomo, J Ninomiya-Tsuji… - … and biophysical research …, 2003 - Elsevier
K Ono, T Ohtomo, J Ninomiya-Tsuji, M Tsuchiya
Biochemical and biophysical research communications, 2003•ElsevierTransforming growth factor-β (TGF-β) is crucially virulent in the progression of fibrotic
disorders. TAK1 (TGF-β activated kinase 1) is one of the mitogen-activated kinase kinase
kinase (MAPKKK) that is involved in TGF-β signal transduction. To elucidate the importance
of TAK1 in TGF-β-induced fibrotic marker expression, we investigated whether dominant
negative TAK1 could suppress TGF-β signaling. Based on the finding that TAB1 (TAK1
binding protein 1) binding to TAK1 is required for TAK1 activation, a minimal portion of TAK1 …
disorders. TAK1 (TGF-β activated kinase 1) is one of the mitogen-activated kinase kinase
kinase (MAPKKK) that is involved in TGF-β signal transduction. To elucidate the importance
of TAK1 in TGF-β-induced fibrotic marker expression, we investigated whether dominant
negative TAK1 could suppress TGF-β signaling. Based on the finding that TAB1 (TAK1
binding protein 1) binding to TAK1 is required for TAK1 activation, a minimal portion of TAK1 …
Transforming growth factor-β (TGF-β) is crucially virulent in the progression of fibrotic disorders. TAK1 (TGF-β activated kinase 1) is one of the mitogen-activated kinase kinase kinase (MAPKKK) that is involved in TGF-β signal transduction. To elucidate the importance of TAK1 in TGF-β-induced fibrotic marker expression, we investigated whether dominant negative TAK1 could suppress TGF-β 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-β 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-β signaling effectively.
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