Article

Signal Transduction through MAP Kinase Cascades

Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder 80309, USA.
Advances in Cancer Research (Impact Factor: 4.26). 02/1998; 74:49-139. DOI: 10.1016/S0065-230X(08)60765-4
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ABSTRACT The chapter introduces the mitogen-activated protein (MAP) kinase (MAPK) module. The identification of MAP kinase pathways exemplifies the power of combining biochemical and genetic approaches to molecular problems. The chapter discusses the mammalian MAPK pathways—ERKl/2 and MKKl/2 pathways—and stress-activated protein kinase pathways. The regulation of MAPK pathways by protein phosphatases is discussed in the chapter describing in detail about dual specificity phosphatases, serinenhreonine phosphatases, and protein tyrosine phosphatases. The chapter explores the cellular substrates of MAP kinases, wherein it discusses about protein kinase substrates for MAPKS, nuclear transcription factors, signaling components, and cytoskeletal proteins. Responses to MAPK pathways, regulation of cell growth and transformation, and regulation of cell differentiation and development have also been summarized in the chapter. The chapter describes the yeast MAPK pathways of saccharomyces cerevisiae (Budding Yeast) and Schizosaccharomyces pombe (Fission Yeast). The chapter provides the description of the intracellular targeting and spatial regulation of MAPK pathway components, signaling complexes, and the nuclear translocation of MAPK and MKK. Eukaryotic MAPK cascades provide excellent examples of signal transduction mechanisms that embody key principles common to many, if not all, signaling pathways. Many fundamental questions remain for future studies to investigate the mechanisms by which these pathways are regulated as well as the cellular responses that they control.

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Available from: Timothy S Lewis, Jul 20, 2015
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    • "Activated Raf phosphorylates mitogen-activated protein kinase kinase (MEK) 1 and 2, which in turn phosphorylate extracellular signal-regulated kinase 1 and 2 (ERK1 and 2). ERKs and their downstream elements can function as transcriptional and translational regulators and promote cellular transformation, proliferation and survivability [28] [29] [30]. In cancers where an activating mutation of Ras protein is absent, the upstream or downstream signaling "
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    • "Those are the extracelluar signal-regulated protein kinase (Erk), c-Jun N-terminal kinase/stress-activated protein kinases (Jnk/Sapk) and p38 [10]. The roles of MAPKs are involved in regulating cell proliferation, cell differentiation and cell apoptosis [11] [12] [13]. MAPK kinase kinase kinase isoform 4 (MAP4K4) is known as a germinal centre protein kinases that belong to the mammalian STE20/MAP4K family [14] [15]. "
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    • "Phosphorylation of plectin S4642 was hence dependent on ERK1/2 and/or ERK5. Nevertheless, they cannot directly phosphorylate plectin S4642, because of their substrate consensus motif incompatible with S4642 (Lewis et al., 1998). ERK1/2 and ERK5 activate several downstream kinases encompassing 90 kDa ribosomal S6 kinases (p90RSKs), mitogen and stress activated kinases (MSKs), and MAP-kinaseinteracting kinases (MNKs) (Cargnello and Roux, 2011). "
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