Antibody Sampler Kits

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).

Four residues (Thr25, Thr222, Ser272 and Thr334) of MAPKAPK-2 are phosphorylated by p38 in an in vitro kinase assay (3). Phosphorylation at Thr222, Ser272 and Thr334 seems to be essential for the activity of MAPKAPK-2 (3). Activated MAPKAPK-2 can in return phosphorylate HSP27 at serines 15, 78 and 82 (3,9). Phosphorylation of HSP27 causes a change in the tertiary structure of HSP27, which shifts from large homotypic multimers to dimmers and monomers (10). It has been illustrated that phosphorylation and increased concentration of HSP27 modulate actin polymerization and reorganization (11,12).

1. Rouse, J. et al. (1994) Cell 78, 1027-1037.
2. Han, J. et al. (1994) Science 265, 808-811.
3. Lee, J.C. et al. (1994) Nature 372, 739-746.
4. Freshney, N.W. et al. (1994) Cell 78, 1039-1049.
5. Raingeaud, J. et al. (1995) J. Biol. Chem. 270, 7420-7426.
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.
11. Landry, . et al. (1992) J. Biol. Chem. 267, 794-803.
12. Rogalla, . et al. (1999) J. Biol. Chem. 274, 18947-18956.
13. Lavoie, J. et al. (1993) J. Biol. Chem. 268, 24210-24214.
14. Rousseau, S. et al. (1997) Oncogene 15, 2169-2177.

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Phospho-p38 MAPK Pathway Sampler Kit

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