Activation of recruited TAK1

Stable Identifier
Reaction [transition]
Gallus gallus
Related Species
Infectious bronchitis virus
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Chicken TAK1 complex proteins TAK1, TAB1, TAB2 and TAB3, confirmed by transcript evidence, show 89%, 88% , 87%, 85% amino acid identity with their human counterparts respectively.

Embryonic fibroblasts and B cells derived from TAK1-deficient mice show reduced NF-kappaB, JNK and p38 activation in response to various TLR ligands. Furthermore, ERK1 and ERK2 activation was also reduced in TAK1-deficient mouse B cells [Sato S et al 2005].

Although there are no experimental data showing a TAK1 functional role in chicken innate immune response, its kinase activity was demonstrated to be essential for BCR (B cell antigen receptor)-mediated IKK and JNK activation in chicken DT40 B cells [Shinohara H et al 2005]. When BCR-mediated NF-kappaB activation was abolished, JNK phosphorylation was completely abolished, while ERK was activated normally in a TAK1-deficient chicken DT40 B cell line.

Thus, TAK1 is believed to activate the IKK complex that leads to NF-kappaB activation. Also TAK1 phosphorylates members of the MAP kinase kinase family, MKK4, MKK3 and MKK6, which subsequently activate JNK and p38. ERK is also activated in response to TLR ligands through the activation of MEK1 and MEK2, although an upstream kinase activating MEK1 and MEK2 in TLR signaling remains unknown.

Polyubiquitinated TRAF6 activates TAK1 by binding to the ubiquitin receptor TAB2 (also known as MAP3K7IP2). This binding leads to autophosphorylation and activation of TAK1.

Literature References
PubMed ID Title Journal Year
11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK

Deng, L, Inoue, J, Akkaraju, GR, Hong, M, Wang, C, Chen, ZJ

Nature 2001
17496917 Ubiquitin-mediated activation of TAK1 and IKK

Xu, M, Adhikari, A, Chen, ZJ

Oncogene 2007
16301747 PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1

Shinohara, H, Sakurai, H, Sanjo, H, Aiba, Y, Hamadate, M, Yasuda, T, Watarai, H, Kurosaki, T

J Exp Med 2005
16260493 TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo

Shim, JH, Steckel, M, Xiao, C, Yamada, G, Ghosh, S, Paschal, AE, Bussey, C, Matsumoto, K, Tanaka, N, Rao, P, Hayden, MS, Akira, S, Bailey, ST, Lee, KY

Genes Dev 2005
Catalyst Activity

protein serine/threonine kinase activity of viral dsRNA : TLR3 : TICAM1 : pUb_TRAF6 :TAB2 :TAB3: TAK1 : TAB1: free_pUb_chain [endosome membrane]

Inferred From
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