MAP Kinase Signaling

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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).

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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.

• Lal, H. et al. (2008) J Mol Cell Cardiol 45, 770-8. Applications: Western Blotting
• Lal, H. et al. (2007) J Mol Cell Cardiol 43, 137-47. Applications: Western Blotting
• Kubo, T. et al. (2009) J Exp Med 206, 1971-82. Applications: Western Blotting

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p38α MAPK (5F11) Mouse mAb

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