Phospho-TAK1 (Thr184/187) Antibody [G4C5]

Application: Reactivity: Human

Lane 1: 293 IL-1R cell, Lane 2: 293 IL-1R cell (IL-1, 10 min)

Usage Information

Dilution
WB1:1000

Application
WB

Reactivity
Human

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
82 kDa

Datasheet & SDS

Biological Description

Specificity
Phospho-TAK1 (Thr184/187) Antibody [G4C5] detects endogenous levels of total TAK1 protein only when it is phosphorylated at Thr184/187.

Clone
G4C5

Synonym(s)
Mitogen-activated protein kinase kinase kinase 7; Transforming growth factor-beta-activated kinase 1 (TGF-beta-activated kinase 1); MAP3K7; TAK1

Background
Phospho-TAK1 (Thr184/187) is the activated form of the serine/threonine kinase TAK1 (MAP3K7), marked by dual phosphorylation within the activation T-loop of its N-terminal kinase domain. This modification is induced by TAB1 binding, which relieves autoinhibition and promotes autophosphorylation, stabilizing TAK1’s active conformation necessary for transmitting innate immune and stress signals. The phosphorylation sites are located between the conserved DFG and APE motifs, ensuring precise ATP binding and substrate access. TAB2 and TAB3 further enhance TAK1 activation by recruiting ubiquitin chains from TRAF6, amplifying signal transduction. Activated phospho-TAK1 serves as a central node for TNF-α, IL-1, and TGF-β pathways, directly phosphorylating IKKβ to trigger NF-κB nuclear translocation and proinflammatory cytokine production, as well as activating MKK4/6/7 to drive JNK and p38 MAPK cascades that regulate apoptosis, survival, and inflammation. Phosphorylation at Thr184/187 is essential for IL-1-induced NF-κB and AP-1 synergy and for optimal IL-6 expression, as mutations at these sites abolish downstream activation even in the presence of TAB1, while phospho-mimetic mutants hyperactivate these pathways. Hyperactive phospho-TAK1 at these residues sustains chronic NF-κB signaling in diseases such as rheumatoid arthritis, inflammatory bowel disease, and cancer, while selective inhibition of Thr184/187 phosphorylation disrupts TAK1 signalosome assembly, suppressing inflammatory cytokine storms and tumor progression.

Background

Phospho-TAK1 (Thr184/187) is the activated form of the serine/threonine kinase TAK1 (MAP3K7), marked by dual phosphorylation within the activation T-loop of its N-terminal kinase domain. This modification is induced by TAB1 binding, which relieves autoinhibition and promotes autophosphorylation, stabilizing TAK1’s active conformation necessary for transmitting innate immune and stress signals. The phosphorylation sites are located between the conserved DFG and APE motifs, ensuring precise ATP binding and substrate access. TAB2 and TAB3 further enhance TAK1 activation by recruiting ubiquitin chains from TRAF6, amplifying signal transduction. Activated phospho-TAK1 serves as a central node for TNF-α, IL-1, and TGF-β pathways, directly phosphorylating IKKβ to trigger NF-κB nuclear translocation and proinflammatory cytokine production, as well as activating MKK4/6/7 to drive JNK and p38 MAPK cascades that regulate apoptosis, survival, and inflammation. Phosphorylation at Thr184/187 is essential for IL-1-induced NF-κB and AP-1 synergy and for optimal IL-6 expression, as mutations at these sites abolish downstream activation even in the presence of TAB1, while phospho-mimetic mutants hyperactivate these pathways. Hyperactive phospho-TAK1 at these residues sustains chronic NF-κB signaling in diseases such as rheumatoid arthritis, inflammatory bowel disease, and cancer, while selective inhibition of Thr184/187 phosphorylation disrupts TAK1 signalosome assembly, suppressing inflammatory cytokine storms and tumor progression.

References
https://pubmed.ncbi.nlm.nih.gov/18617512/ https://pubmed.ncbi.nlm.nih.gov/25028512/

Reference Table for Selecting PVDF Membrane Pore Size Specifications

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%