Cell Signaling Technology

Product Pathways - MAPK Signaling

Phospho-TAK1 (Thr187) Antibody #4536

Applications Reactivity Sensitivity MW (kDa) Source
W H (M) (R) (C) (B) (X) (Z) Endogenous 82 Rabbit

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human  M=Mouse  R=Rat  C=Chicken  B=Bovine  X=Xenopus  Z=Zebrafish
Species cross-reactivity is determined by Western blot.

Protocols

Specificity / Sensitivity

Phospho-TAK1 (Thr187) Antibody detects endogenous levels of TAK1 only when phosphorylated at threonine 187.

Source / Purification

Polyclonal antibodies are produced by immunizing rabbits with a synthetic phospho-peptide (KLH-coupled) corresponding to residues surrounding Thr187 of human TAK1. Antibodies are purified by protein A and affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from 293IL-1R cells, untreated or treated with IL-1beta and Calyculin A for the indicated times, using Phospho-TAK1 (Thr187) Antibody.

Background

TAK1 is a mitogen-activated protein kinase kinase kinase that can be activated by TGFbeta, bone morphogenetic protein and other cytokines including IL-1 (1,2). In vivo activation of TAK1 requires association with TAK1 binding protein 1 (TAB1), which triggers phosphorylation of TAK1 (3,4). Another adaptor protein, TAB2, links TAK1 with TRAF6 and mediates TAK1 activation upon IL-1 stimulation (5). Once activated, TAK1 phosphorylates MAPK kinases MKK4 and MKK3/6, which activate p38 MAPK and JNK, respectively. In addition, TAK1 activates the NF-kappaB pathway by interacting with TRAF6 and phosphorylating the NF-kappaB inducing kinase (NIK) (2).

TAK1 activation requires multiple phosphorylations in its activation loop. Mutation of Thr187 and Thr184, residues located in the activation loop of TAK1, impairs phosphorylation of both TAK1 and TAB1 and reduces the kinase activity of TAK1, suggesting that autophosphorylation of these residues is necessary for TAK1 activation (4).

  1. Yamaguchi, K. et al. (1995) Science 270, 2008-2011.
  2. Ninomiya-Tsuji, J. et al. (1999) Nature 398, 252-256.
  3. Shibuya, H. et al. (1996) Science 272, 1179-1182.
  4. Sakurai, H. et al. (2000) FEBS Lett. 474, 141-145.
  5. Takaesu, G. et al. (2000) Mol. Cell 4, 649-658.
  6. Sakurai, H. et al. (2000) FEBS 474, 141-145.

Application References

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Companion Products

This product is for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.

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