The ERK Cascade: Distinct Functions within Various Subcellular Organelles
Open accessAbstract
The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade is a central signaling pathway that regulates a wide variety of stimulated cellular processes, including mainly proliferation, differentiation, and survival, but apoptosis and stress response as well. The ability of this linear cascade to induce so many distinct and even opposing effects after various stimulations raises the question as to how the signaling specificity of the cascade is regulated. Over the past years, several specificity-mediating mechanisms have been elucidated, including temporal regulation, scaffolding interactions, crosstalks with other signaling components, substrate competition, and multiple components in each tier of the cascade. In addition, spatial regulation of various components of the cascade is probably one of the main ways by which signals can be directed to some downstream targets and not to others. In this review, we describe first the components of the ERK1/2 cascade and their mode of regulation by kinases, phosphatases, and scaffold proteins. In the second part, we focus on the role of MEK1/2 and ERK1/2 compartmentalization in the nucleus, mitochondria, endosomes, plasma membrane, cytoskeleton, and Golgi apparatus. We explain that this spatial distribution may direct ERK1/2 signals to regulate the organelles' activities. However, it can also direct the activity of the cascade's components to the outer surface of the organelles in order to bring them to close proximity to specific…
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c-fos expression after PHx is dependent on presence of senescent cells and ERK activation.
“the expression of c-fos, an ERK-regulated gene that can promote hepatocyte cell cycle reentry through the regulation of cyclin D1 (59, 60), was elevated after PHx but eliminated by ABT263 or SCH772984, indicating that c-fos expression after PHx is dependent on the presence of senescent cells and ERK activation”
From Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2 (2022) · cites this paper as [59]
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- Authors
- Wortzel, I., & Seger, R.
- Affiliations
- Weizmann Institute of Science (IL)
- ORCID
- Venue
- Genes & Cancer
- Publisher
- SAGE Publications
- Published
- 2011-03-01
- Volume
- 2
- Issue
- 3
- Pages
- 195-209
- ISSN
- 1947-6019 (ISSN-L)
- 1947-6027
- PMC
- PMC3128630
- OpenAlex
- W1969179779
- Cited by
- 563
- References
- 12
- Citations by year
- 2026: 29 · 2025: 43 · 2024: 45 · 2023: 38 · 2022: 54 · 2021: 40 · 2020: 42 · 2019: 34 · 2018: 39 · 2017: 24 · 2016: 34 · 2015: 37 · 2014: 40 · 2013: 31 · 2012: 32
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Cancer (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Cancer Research Fund
- Yale University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- MEK1/2, signaling specificity, subcellular compartmentalization, scaffold proteins, substrate competition, crosstalk, spatial regulation of signaling, Golgi apparatus, mitochondria, endosomes, cytoskeleton, nuclear localization, phosphatase, kinase regulation
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