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Western blot analysis of extracts from NIH/3T3 cells, untreated or sorbitol-treated for 30 minutes with or without SB203580 pre-treatment (1 hr.), using Phospho-MAPKAPK-2 (Thr222) Antibody #3044 (upper) or MAPKAPK-2 Antibody #3042 (lower).

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Western blot analysis of extracts from NIH/3T3 cells, untreated or sorbitol-treated for 30 minutes with or without SB203580 pre-treatment (1 hr.), using Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP® Rabbit mAb #4511 (upper) or p38 MAPK Antibody #9212 (lower).

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Molecular weight: 377.43

Molecular formula: C21H16FN3OS

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Product Usage Information

SB203580 is supplied as a lyophilized white powder. For 10 mM stock, resuspend 5 mg of the inhibitor in 1.32 ml DMSO. Aliquot and freeze at -20ºC to avoid multiple freeze/thaw cycles which can degrade the inhibitor. For experiments with cultured cells, we recommend pre-treating the cells with SB203580 at 10 µM for one to two hours prior to stimulation. This product is for in vitro research use only and is not intended for use in humans or animals.


Storage: Store lyophilized or in solution at -20ºC, desiccated. Protect from light. In lyophilized form, the chemical is stable for 24 months. Once in solution, use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Product Description

Molecular Weight:

377.43 g/mol


Purity:

>98%


Molecular Formula:

C21H16FN3OS


p38 MAP kinase (MAPK), also called RK (1) or CSBP (2), is the mammalian orthologue of the yeast HOG kinase that participates in a signaling cascade controlling cellular responses to cytokines and stress (1-4). Four isoforms of p38 MAPK, p38α, β, γ (also known as Erk6 or SAPK3), and δ (also known as SAPK4) have been identified. Similar to the SAPK/JNK pathway, p38 MAPK is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharide (LPS), UV light, and growth factors (1-5). MKK3, MKK6, and SEK activate p38 MAPK by phosphorylation at Thr180 and Tyr182. Activated p38 MAPK has been shown to phosphorylate and activate MAPKAP kinase 2 (3) and to phosphorylate the transcription factors ATF-2 (5), Max (6), and MEF2 (5-8).

SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole) is a selective inhibitor of p38 MAPK. This compound inhibits the activation of MAPKAPK-2 by p38 MAPK and subsequent phosphorylation of HSP27 (9). SB203580 inhibits p38 MAPK catalytic activity by binding to the ATP-binding pocket, but does not inhibit phosphorylation of p38 MAPK by upstream kinases (10).


1.  Han, J. et al. (1994) Science 265, 808-11.

2.  Raingeaud, J. et al. (1995) J. Biol. Chem. 270, 7420-7426.

3.  Rouse, J. et al. (1994) Cell 78, 1027-1037.

4.  Lee, J.C. et al. (1994) Nature 372, 739-46.

5.  Freshney, N.W. et al. (1994) Cell 78, 1039-49.

6.  Zervos, A.S. et al. (1995) Proc. Natl. Acad. Sci. USA 92, 10531-10534.

7.  Zhao, M. et al. (1999) Mol. Cell. Biol. 19, 21-30.

8.  Yang, S.H. et al. (1999) Mol. Cell. Biol. 19, 4028-4038.

9.  Cuenda, A. et al. (1995) FEBS Lett 364, 229-33.

10.  Kumar, S. et al. (1999) Biochem Biophys Res Commun 263, 825-31.



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