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Control of MAPK Signaling by Ste20- and Ste11-Like Kinases

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Book cover Signaling Networks and Cell Cycle Control

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Mammalian mitogen-activated protein kinases (MAPKs) were identified biochemically during the late 1980s (1,2). In 1990, mammalian p44 MAPK was cloned and referred to as extracellular signal-regulated kinase (ERK) (3). In parallel, MAPK pathways were being identified by genetic selection in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, the fly Drosophila melanogaster, and the worm Caenorhabditis elegans (4–6). Molecular cloning and functional characterization has defined a growing family of MAPKs in all eukaryotic organisms. MAPKs represent a family of serine/threonine kinases that are uniquely activated by dual phosphorylation of a threonine and tyrosine in a Thr-X-Tyr motif in the activation loop of the kinase domain, where X is an amino acid that varies among different MAPK family members. Eukaryotic cells express multiple MAPKs. For example, to date the number of MAPKs identified includes 12 in mammals, 6 in S.cerevisiae, 4 in S.pombe, 4 in C.elegans, and 3 in D. melanogaster. All the MAPKs characterized to date are members of a module composed of three protein kinases that form a sequential activation pathway (Fig. 1). The three component module consists of a MAPK kinase kinase (MKKK), MAPK kinase (MKK), and the MAPK. When the MKKK is activated, it phosphorylates and activates a specific MKK. The MKK, in turn, phosphorylates and activates a specific MAPK. In many instances, this three component module is regulated by a MAPK kinase kinase kinase (MKKKK). As discussed below, different MAPKs are involved in regulating specific cellular functions including mitosis, differentiation, challenge by cytokines and adaptation to stress such as nutrient starvation, osmotic imbalance, irradiation, and changes in redox state of the cell.

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Authors
  1. Gary R. Fanger
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  2. Thomas K. Schlesinger
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  3. Gary L. Johnson
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Editors and Affiliations

  1. Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    J. Silvio Gutkind PhD

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Fanger, G.R., Schlesinger, T.K., Johnson, G.L. (2000). Control of MAPK Signaling by Ste20- and Ste11-Like Kinases. In: Gutkind, J.S. (eds) Signaling Networks and Cell Cycle Control. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-218-0_11

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  • DOI: https://doi.org/10.1007/978-1-59259-218-0_11

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