Regulation of the TAK1 Signaling Pathway by Protein Phosphatase 2C

Protein Phosphatase 6 Down-regulates TAK1 Kinase Activation in the IL-1 Signaling Pathway

“…In general, the level of protein phosphorylation is controlled by the balanced activities of protein kinases and protein phosphatases. Indeed, TAK1 activity is known to be regulated by protein phosphatase PP2C family members in the unstimulated state (24,25). In this study, we found that inhibition of type 2A protein phosphatases results in hyperphosphorylation and hyperactivation of TAK1 in response to IL-1 stimulation.…”

“…The mechanism by which TAK1 is down-regulated has not yet been elucidated, but it is likely to involve protein phosphatases. Indeed, both TAK1 phosphorylation and activation are regulated by PP2C family (also known as MPP) phosphatases, which participate in silencing TAK1 basal activity in the unstimulated state (24,25). To further address which protein phosphatases reverse stimuliinduced TAK1 activation, we examined the effects of protein phosphatase inhibitors on IL-1-induced TAK1 phosphorylation.…”

The Dual-specificity Phosphatase DUSP14 Negatively Regulates Tumor Necrosis Factor- and Interleukin-1-induced Nuclear Factor-κB Activation by Dephosphorylating the Protein Kinase TAK1

“…Previous studies have suggested that phosphorylation and dephosphorylation are critically involved in regulation of several key components of TNF-or IL-1-triggered NF-B signaling pathways, such as TAK1, IKK␤, and p65 (17,18). Previous reports have demonstrated that protein phosphatases 6 and 2C are involved in suppression of TNF-and IL-1-induced TAK1 activation (15,18,22,23). In this study, we found that overexpression of DUSP14 dephosphorylated TAK1 at Thr-187, whereas knockdown of DUSP14 potentiated this phosphorylation in unstimulated and TNF-or IL-1-stimulated cells.…”

Transforming Growth Factor-β (TGF-β1) Activates TAK1 via TAB1-mediated Autophosphorylation, Independent of TGF-β Receptor Kinase Activity in Mesangial Cells

“…Expression Constructs-Mammalian expression constructs for HA-tagged wild type TAK1 (HA-TAK1) and kinase-deficient mutant TAK1 (HA-TAK1-KD (K63W), FLAG-TAB1, and Myc-TAB1 were kindly provided by K. Matsumoto (Nagoya University) (60). FLAG-tagged wild type TAK1 (FLAG-TAK1), kinase-deficient mutant TAK1 (FLAG-TAK1-KD (K63W)), and C-terminal-truncated mutant TAK1 (FLAG-TAK1⌬C) were kindly provided by G. Gross (42).…”