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Differential regulation and properties of MAPKs
Abstract
Mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs including embryogenesis, proliferation, differentiation and apoptosis based on cues derived from the cell surface and the metabolic state and environment of the cell. In mammals, there are more than a dozen MAPK genes. The best known are the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK(1-3)) and p38(alpha, beta, gamma and delta) families. ERK3, ERK5 and ERK7 are other MAPKs that have distinct regulation and functions. MAPK cascades consist of a core of three protein kinases. Despite the apparently simple architecture of this pathway, these enzymes are capable of responding to a bewildering number of stimuli to produce exquisitely specific cellular outcomes. These responses depend on the kinetics of their activation and inactivation, the subcellular localization of the kinases, the complexes in which they act, and the availability of substrates. Fine-tuning of cascade activity can occur through modulatory inputs to cascade component from the primary kinases to the scaffolding accessory proteins. Here, we describe some of the properties of the three major MAPK pathways and discuss how these properties govern pathway regulation and activity.
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“The D-motif is also found in phosphatases, substrates, and scaffold proteins (Raman et al., 2007).”
From Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases (2012) · cites this paper as Raman et al., 2007
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Parker, C. G., Hunt, J. B., Diener, K., McGinley, M., Soriano, B., Keesler, G. A., Bray, J., Yao, Z., Wang, X. S., Kohno, T., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9250 · Cited by 70
Cho, J., & Tsichlis, P. N. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409856102 · Cited by 63
Cell adhesion differentially regulates the nucleocytoplasmic distribution of active MAP kinases
Aplin, A. E., Hogan, B. P., Tomeu, J., & Juliano, R. L. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.13.2781 · Cited by 61
c-Jun-NH2 Kinase (JNK) Contributes to the Regulation of c-Myc Protein Stability
Alarcon-Vargas, D., & Ronai, Z. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312054200 · Cited by 59
Court, N. W., dos Remedios, C. G., Cordell, J., & Bogoyevitch, M. A. (2002) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2001.1523 · Cited by 59
Mapping ERK2-MKP3 Binding Interfaces by Hydrogen/Deuterium Exchange Mass Spectrometry
Zhou, B., Zhang, J., Liu, S., Reddy, S., Wang, F., & Zhang, Z. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608916200 · Cited by 56
BuCy RAFs drive cells into MEK addiction
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Protein Phosphatase 4 Is a Positive Regulator of Hematopoietic Progenitor Kinase 1
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Sanz‐Moreno, V., Casar, B., & Crespo, P. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.9.3079-3090.2003 · Cited by 45
POSH, a scaffold protein for JNK signaling, binds to ALG‐2 and ALIX in Drosophila
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The Nuclear Localization of ERK2 Occurs by Mechanisms Both Independent of and Dependent on Energy
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Self-citationCyclic AMP Selectively Uncouples Mitogen-Activated Protein Kinase Cascades from Activating Signals
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Flagged first, then by citations
1 of the 122 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
Ray, P. D., Huang, B.-W., & Tsuji, Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.008 · Cited by 4,373
Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases
Cargnello, M., & Roux, P. P. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00031-10 · Cited by 3,274
ERK1/2 MAP kinases: Structure, function, and regulation
Roskoski, R. J. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.04.005 · Cited by 1,719
Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis
Sinha, K., Das, J., Pal, P. B., & Sil, P. C. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1034-4 · Cited by 1,643
Dhanasekaran, D. N., & Reddy, E. P. (2008) · Oncogene · doi:10.1038/onc.2008.301 · Cited by 1,558
Metadata
- Authors
- Raman, M., Chen, W., & Cobb, M. H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Cobb, M H
- Venue
- Oncogene
- Published
- 2007-05-14
- Volume
- 26
- Issue
- 22
- Pages
- 3100-3112
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1998809668
- Cited by
- 1,430
- References
- 122
- Citations by year
- 2026: 21 · 2025: 38 · 2024: 37 · 2023: 74 · 2022: 69 · 2021: 53 · 2020: 69 · 2019: 68 · 2018: 65 · 2017: 70 · 2016: 83 · 2015: 64 · 2014: 110 · 2013: 105 · 2012: 101
- FWCI
- 41.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM53032, R01GM056498, R01GM053032, GM 56498)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-34128)
- 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, ERK1/2, c-Jun N-terminal kinase, p38 MAPK, ERK3, ERK5, subcellular localization, scaffold proteins, signal transduction regulation
- MeSH terms
- Animals, Humans, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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