Cited by 1,600Protein Kinase Regulation and GTPase SignalingMelanoma and MAPK PathwaysProtein Tyrosine Phosphatases

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Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers

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Schaeffer, Hans J., Weber, Michael J.·1999·Molecular and Cellular Biology

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Abstract

Signal transduction networks allow cells to perceive changes in the extracellular environment and to mount an appropriate response. Mitogen-activated protein kinase (MAPK) cascades are among the most thoroughly studied of signal transduction systems and have been shown to participate in a diverse array of cellular programs, including cell differentiation, cell movement, cell division, and cell death. A key question in studies of this cascade is, how does a ubiquitously activated regulatory enzume generate a specific and biologically appropriate cellular response? In this review we describe recent findings that provide insight into ways that the regulation, structure, and localization of MAPKs and the participation of adapters and scaffolds can help determine biological outcomes. MAPK cascades are evolutionarily conserved in all eucaryotes and play a key role in the regulation of gene expression as well as cytoplasmic activities. They typically are organized in a three-kinase architecture consisting of a MAPK, a MAPK activator (MEK, MKK, or MAPK kinase), and a MEK activator (MEK kinase [MEKK] or MAPK kinase kinase). Transmission of signals is achieved by sequential phosphorylation and activation of the components specific to a respective cascade. In the yeast Saccharomyces cerevisiae, five MAPK modules have been described; they regulate mating, filamentation, high-osmolarity responses, cell wall remodeling, and sporulation (Fig. (Fig.1A)1A) (reviewed in references 56 and 77). In mammalian systems five distinguishable MAPK modules have been identified so far (Fig. (Fig.1B).1B). These include the extracellular signal-regulated kinase 1 and 2 (ERK1/2) cascade, which preferentially regulates cell growth and differentiation, as well as the c-Jun N-terminal kinase (JNK) and p38 MAPK cascades, which function mainly in stress responses like inflammation and apoptosis (reviewed in references 57, 74, and 103). Moreover, MAPK pathways control several developmental programs, such as morphogenesis and spatial patterning in Dictyostelium amoebae (17, 45), eye development in Drosophila melanogaster (124), vulva induction in Caenorhabditis elegans (113), and T-cell development in mammals (31). FIG. 1 Schematic overview of MAPK modules. (A) In S. cerevisiae, five MAPK modules regulate mating, filamentation, high-osmolarity responses, cell wall remodeling, and sporulation. (B) Mammalian MAPK modules regulate cell growth, differentiation, stress responses, ... Individual MAPK modules generally can signal independently from each other, and this specificity is manifested in distinct physiologic responses. This is most obvious when studying MAPK signaling in S. cerevisiae. Here a particular extracellular event characteristically activates a specific MAPK module and initiates a unique cellular program (reviewed in references 56 and 77). For example, stimulation of cells with pheromone leads to the activation of the pheromone response pathway (STE11, STE7, and FUS3) (Fig. (Fig.2),2), which ultimately results in cell cycle arrest and the induction of mating-specific genes. However, related MAPKs whose modules share some components with the pheromone response pathway are not affected by pheromone stimulation but are activated only in response to the appropriate stimulus. For example, under conditions of high osmolarity Ste11 can lead to activation of Hog1 but does not induce mating-specific genes. Conversely, conditions that activate the filamentation pathway (which utilizes STE11 and STE7) induce only genes that regulate filamentous growth without triggering pheromone responses or responses to high osmolarity. These observations suggest that yeast cells have developed efficient mechanisms to generate pathway specificity and to successfully suppress cross talk, even when individual components participate in more than one signaling pathway. FIG. 2 Scaffold and adapter molecules in MAPK pathways. MAPK scaffolds and adapters (gray shading) are thought to promote the formation of oligomeric protein complexes with components that function in a specific MAPK module. Scaffolds have been identified in ... In metazoan cells the problem is more complex because each cell is simultaneously exposed to multiple extracellular signals and must integrate these inputs to choose an appropriate response. Thus, the biological context of a signal plays a determinative role in the way that MAPK activation is interpreted. For example, although ERKs generally regulate cell growth and cell differentiation and JNKs participate in a stress response, this is not always the case and in certain cell types activation of JNKs can induce proliferation (110). This indicates that in mammalian systems physiologic responses associated with a certain MAPK module can be cell type specific. Moreover, in PC12 cells, transient stimulation of the ERK cascade leads to proliferation whereas sustained stimulation leads to differentiation,

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Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation
Marshall, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90401-8 · Cited by 3,906
JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
Dérijard, B., Hibi, M., Wu, I.-H., Barrett, T., Su, B., Deng, T., Karin, M., & Davis, R. J. (1994) · Cell · doi:10.1016/0092-8674(94)90380-8 · Cited by 3,188
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Robinson, M. J., & Cobb, M. H. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80061-0 · Cited by 2,489
Signaling Through Scaffold, Anchoring, and Adaptor Proteins
Pawson, T., & Scott, J. D. (1997) · Science · doi:10.1126/science.278.5346.2075 · Cited by 2,256
Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
de Rooij, J., Zwartkruis, F. J. T., Verheijen, M. H. G., Cool, R. H., Nijman, S. M. B., Wittinghofer, A., & Bos, J. L. (1998) · Nature · doi:10.1038/24884 · Cited by 1,970
Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase
Kato, S., Endoh, H., Masuhiro, Y., Kitamoto, T., Uchiyama, S., Sasaki, H., Masushige, S., Gotoh, Y., Nishida, E., Kawashima, H., et al. (1995) · Science · doi:10.1126/science.270.5241.1491 · Cited by 1,964
Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells
Cowley, S. A. (1994) · Cell · doi:10.1016/0092-8674(94)90133-3 · Cited by 1,959
Mammalian Ras interacts directly with the serine/threonine kinase raf
Vojtek, A. B., Hollenberg, S. M., & Cooper, J. A. (1993) · Cell · doi:10.1016/0092-8674(93)90307-c · Cited by 1,934
Crystal Structure of the Catalytic Subunit of Cyclic Adenosine Monophosphate-Dependent Protein Kinase
Knighton, D. R., Zheng, J., Eyck, L. F. T., Ashford, V. A., Xuong, N., Taylor, S. S., & Sowadski, J. M. (1991) · Science · doi:10.1126/science.1862342 · Cited by 1,764
Signal Transduction through MAP Kinase Cascades
Lewis, T. S., Shapiro, P. S., & Ahn, N. G. (1998) · Advances in cancer research · doi:10.1016/s0065-230x(08)60765-4 · Cited by 1,759

Show all 144 references

Research works printed but not linked: 4

10.1128/mcb.12.3.915-927.1992 · DOI
10.1128/mcb.14.12.8212-8218.1994 · DOI
10.1128/mcb.14.10.6683-6688.1994 · DOI
10.1128/mcb.14.3.1594-1602.1994 · DOI

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Authors: Schaeffer, H. J., & Weber, M. J.
Affiliations: University of Virginia (US)
ORCID: Schaeffer, Hans J.
Weber, Michael J.
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1999-04
Volume: 19
Issue: 4
Pages: 2435-2444
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.19.4.2435
PMC: PMC84036
OpenAlex: W1899552864
Semantic Scholar: bf5b29dd374f8bafd23fa8c6a133d764aa27c83f
Cited by: 1,600
References: 144
Citations by year: 2026: 12 · 2025: 12 · 2024: 24 · 2023: 32 · 2022: 23 · 2021: 28 · 2020: 19 · 2019: 37 · 2018: 43 · 2017: 27 · 2016: 31 · 2015: 41 · 2014: 42 · 2013: 49 · 2012: 61
FWCI: 9.18
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01gm047332-08, 1r01ca076500-01a1)
U.S. Public Health Service
National Cancer Institute (CA-39076, CA76500)
National Institute of General Medical Sciences (GM-47332)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: mitogen-activated protein kinase, MAPK signaling, signal transduction, ERK1/2, JNK, p38 MAPK, adaptor proteins, Saccharomyces cerevisiae, cell differentiation, stress response, apoptosis, cell growth and division
MeSH terms: Carrier Proteins, Cell Compartmentation, Fungal Proteins, Models, Biological, Morphogenesis, Protein Kinases, Saccharomyces cerevisiae, Substrate Specificity, Time Factors, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, Receptor Cross-Talk, Mitogen-Activated Protein Kinase Kinases, Saccharomyces cerevisiae Proteins, Adaptor Proteins, Signal Transducing

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Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers

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