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Use of Inhibitors in the Study of MAP Kinases

Part of the Methods in Molecular Biology book series (MIMB,volume 661)

Abstract

The mitogen-activated protein (MAP) kinases are ubiquitous intracellular signaling proteins that respond to a variety of extracellular signals and regulate most cellular functions including proliferation, apoptosis, migration, differentiation, and secretion. The four major MAP kinase family members, which include the ERK1/2, JNK, p38, and ERK5 proteins, coordinate cellular responses by phosphorylating and regulating the activity of dozens of substrate proteins involved in transcription, translation, and changes in cellular architecture. Uncontrolled activation of the MAP kinases has been implicated in the initiation and progression of a variety of cancers and inflammatory disorders. As such, the ability to manipulate the activity of MAP kinase proteins with specific pharmacological inhibitors has received much attention as research tools for understanding basic mechanisms of cellular functions and for clinical tools to treat diseases. A variety of pharmacological inhibitors have been developed to selectively block MAP kinases directly or indirectly through targeting upstream regulators. This chapter will provide an overview of some of the current inhibitors that target MAP kinase signaling pathways and provide methodology on how to use selective MAP kinase inhibitors and immunoblotting techniques to monitor and quantify phosphorylation of MAP kinase substrates.

Key words

  • Mitogen-activated protein kinase
  • Extracellular signal-regulated kinase
  • c-Jun N-terminal kinase
  • p38 MAP kinase
  • U0126
  • SB203580

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Acknowledgements

The authors would like to thank Kimberly Still for technical assistance. This work was supported by the National Institutes of Health (CA120215).

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Correspondence to Paul Shapiro .

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Burkhard, K., Shapiro, P. (2010). Use of Inhibitors in the Study of MAP Kinases. In: Seger, R. (eds) MAP Kinase Signaling Protocols. Methods in Molecular Biology, vol 661. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-795-2_6

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  • DOI: https://doi.org/10.1007/978-1-60761-795-2_6

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-794-5

  • Online ISBN: 978-1-60761-795-2

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