Cell Signaling Technology

Product Pathways - MAPK Signaling

Phospho-TAK1 (Ser412) Antibody #9339

TAK-1   TAK1  

No. Size Price
9339S 100 µl ( 10 western blots ) ¥3,900.00 现货查询 购买询价
9339 carrier free & custom formulation / quantityemail request
Applications Dilution Species-Reactivity Sensitivity MW (kDa) Isotype
W 1:1000 Human,Mouse,Rat, Endogenous 82 Rabbit
IP 1:50

Species cross-reactivity is determined by western blot.

Applications Key: W=Western Blotting, IP=Immunoprecipitation,

Specificity / Sensitivity

Phospho-TAK1 (Ser412) Antibody detects endogenous levels of TAK1 only when phosphorylated at serine 412.

Phospho-TAK1 (Ser412) Antibody兔多抗能够检测内源性Ser412位点磷酸化的TAK1蛋白水平。

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding serine 412. Antibodies are purified by protein A and peptide affinity chromatography.

该多克隆抗体是采用合成的与人源TAK1蛋白Ser412位点周围残基相一致的磷酸化肽段免疫动物而获得。该抗体经蛋白A和肽亲和层析纯化。

Western Blotting

Western Blotting

Western blot analysis of extracts from K562 cells treated with or without lambda phosphatase, using Phospho-TAK1 (Ser412) Antibody #9339 (left) or TAK1 Antibody #4505 (right).western blot方法检测细胞提取物:lambda磷酸酶处理和未处理的K562细胞。使用的抗体是Phospho-TAK1 (Ser412) Antibody #9339 (左侧)和TAK1 Antibody #4505 (右侧)。

Western Blotting

Western Blotting

Western blot analysis of extracts from K562 (human), C2C12 (mouse) and C6 (rat) cell lines, using Phospho-TAK1 (Ser412) Antibody.western blot方法检测细胞提取物:K562 (人源), C2C12 (小鼠) 和C6 (大鼠)细胞系。使用的抗体是Phospho-TAK1 (Ser412) Antibody。

Western Blotting

Western Blotting

Western blot analysis of extracts from HeLa cells co-treated with and without 100nM Calyculin A (#9902) and 20 ng/mL hIL-1β (#8900) for 10 min., and transfected with and without 100nM SignalSilence® TAK1 siRNA I (#6317) using Phospho-TAK1 (Ser412) Antibody #9339 (top) and β-actin (13E5) Rabbit mAb #4970 (bottom).

Background

TAK1 is a mitogen-activated protein kinase kinase kinase that can be activated by TGF-β, 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-κB pathway by interacting with TRAF6 and phosphorylating the NF-κB inducing kinase (NIK) (2).

TAK1是MAPKKK家族中的成员,由TGF-β、骨形态生成蛋白和包括IL-1在内的细胞因子所激活(1,2)。在体内,TAK1的活化需要它与TAK1结合蛋白1 (TAB1)的结合,这种结合能够使TAK1蛋白磷酸化(3,4)。另一个接头蛋白TAB2能够将TAK1与TRAF6连接起来,调节IL-1刺激引起的TAK1的活化(5)。一经激活,TAK1能够磷酸化MAPK激酶MKK4和MKK3/6,MKK4和MKK3/6再分别激活JNK和p38 MAPK。另外,TAK1能够激活NF-κB通路,这是通过与TRAF6的相互作用及对NF-κB诱导激酶(NIK)的磷酸化实现的 (2)。

TAK1 activation requires multiple phosphorylations in its activation loop. Mutations at 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). TAK1 is also phosphorylated at Ser412 in a PKA-dependent manner (6). A mutation of Ser412 to alanine acts as a dominant negative for PKA-enhanced degradation of IκBα, phosphorylation of p38 MAPK and prostaglandin E2-enhances osteoclastic differentiation in RAW264.7 cells (6).

TAK1的活化需要活化环内的多位点磷酸化。定位于TAK1活化环内的Thr187和Thr184位点的突变,会影响TAK1、TAB1的磷酸化,降低TAK1的激酶活性,暗示了这些位点的自磷酸化是TAK1活化所必需的(4)。TAK1蛋白的Ser412位点也以一种PKA依赖型方式被磷酸化(6)。Ser412位点突变为丙氨酸后,明显抑制了RAW264.7细胞中的PKA增强的IκBα降解、p38 MAPK的磷酸化和前列腺素E2增强的破骨细胞的分化(6)。

  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. Kobayashi, Y. et al. (2005) J Biol Chem 280, 11395-403.

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Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.

Cell Signaling Technology® is a trademark of Cell Signaling Technology, Inc.

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