RIP2 subjected to poly-ubiquitination (pUb) by E3 ligases or linear ubiquitin chain assembly complex (LUBAC) interacts with TGF-beta-activated kinase 1 (TAK1
) and I[kappa]B kinase (IKK) complex to induce nuclear translocation of nuclear factor-[kappa]B (NF-[kappa]B) subunits.
A key protein in the process is TAK1
that acts in the noncanonical pathway of TGF-[beta] [6, 7].
When the protein TAK1
is reduced, satellite stem cells do not vigorously self-renew and many eventually die.
Pathway#: 1 = cell extracellular matrix interactions; 2 = alpha-linolenic acid metabolism; 3 = metabolism of lipids and lipoproteins; 4 = VEGF signaling pathway; 5=P75NTR recruits signaling complexes; 6 = endocytosis; 7 = P75NTR signals via NFKB; 8 = hormone ligand binding receptors; 9 = set pathway; 10 = linoleic acid metabolism; 11 = notch HLH transcription pathway; 12 = long term depression; 13 = FC epsilon RI signaling pathway; 14 = AKAP centrosome pathway; 15 = NA CL dependent neurotransmitter transporters; 16 = activated TAK1
mediates P38 MAPK activation; 17 = ABC transporters; 18 = amino acid transport across the plasma membrane; 19 = amyotrophic lateral sclerosis (ALS); 20 = other glycan degradation.
Dependiendo de la naturaleza del adaptador que se emplee, este se une a la cinasa asociada al receptor de IL-1 (IRAK4, IRAK1, IRAK2, TBK1 y IKKs), las cuales, a su vez, se unen al factor asociado al receptor del TNF-6 (TRAF-6) para activarlo y estimular a TAK1
; esta cinasa pone en marcha la senalizacion por la proteina cinasa MAKK, quien fosforila a otras cinasas como JNK para generar la activacion y translocacion de factores nucleares como el PA-1 y el NF-kB, con la consecuente transcripcion de genes que codifican para citoquinas proinflamatorias.
A range of MAP3Ks have been implicated in the activation of the p38 MAPK pathway, including MLKs (mixed-lineage kinases), TAK1
(transforming growth factor [beta] activated kinase 1), ASK1 (apoptosis signal-regulating kinase 1), TAO (thousand-and-one amino acid), DLK1 (dual-leucine-zipper-bearing kinase 1) MEKKs, and ZAK1 (leucine zipper and sterile-[alpha] motif kinase 1) (Figure 1).
Heat shock protein 90 (Hsp90) regulates the stability of transforming growth factor beta-activated kinase 1 (TAK1
) in interleukin-1beta-induced cell Mol Immunol.
: A Potential New Pathway and Drug Delivery Method
The researchers tested several agents known to inhibit the activity of molecules in the WNT2 pathway their results implied was associated with pancreatic cancer and found that inhibition of TGF-beta activated kinase 1 (TAK1
) prevented metastasis-associated activities in cultured CTCs.
TRAF6 acts as an ubiquitin ligase E and activates the transforming growth factor (TGF) p-activated kinase 1 (TAK1
) complex and its subunits the TAK1-binding protein-(TAB) 1 and TAB2/ 3, responsible for the phosphorylation of NF-kappaB essential modulator (NEMO), which results in the activation of the kinase complexes constituted by inhibitor of kappaB (I[kappa]B) and IkappaB kinase (IkK) and in the degradation of phosphorylated IkB6.
The MAPK kinase kinase TAK1
plays a central role in coupling the interleukin-1 receptor to both transcriptional and RNA-targeted mechanisms of gene regulation.