Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases

  title={Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases},
  author={Gary L. Johnson and Razvan Lapadat},
  pages={1911 - 1912}
Multicellular organisms have three well-characterized subfamilies of mitogen-activated protein kinases (MAPKs) that control a vast array of physiological processes. These enzymes are regulated by a characteristic phosphorelay system in which a series of three protein kinases phosphorylate and activate one another. The extracellular signal–regulated kinases (ERKs) function in the control of cell division, and inhibitors of these enzymes are being explored as anticancer agents. The c-Jun amino… 

The Role of Specific Mitogen-Activated Protein Kinase Signaling Cascades in the Regulation of Steroidogenesis

The current level of understanding concerning the roles of the MAPK signaling cascades in the regulation of StAR expression and steroidogenesis in different steroidogenic cell models is summarized.

Mitogen-activated protein kinases in apoptosis regulation

The regulation of apoptosis by MAPKs is more complex than initially thought and often controversial, and it is critically point out the multiple roles ofMAPKs.

Mitogen-Activated Protein Kinase-Activated Protein Kinases and Metastasis

This review summarizes potential small inhibitors against MAPK-activating protein kinases that may find their way in cancer therapy and focuses on the specific roles of MAPK -activatingprotein kinases in metastasis.

Differential regulation and properties of MAPKs

Some of the properties of the three major MAPK pathways are described and discussed and how these properties govern pathway regulation and activity are discussed.

Role of mitogen-activated protein kinase kinase kinases in signal integration

How the MKKK ‘hub’ function regulates the specificity of MAPK activation is described, highlighting MKKks as targets for therapeutic intervention in cancer and other diseases.

Role of mitogen-activated protein kinase phosphatases (MKPs) in cancer

  • Gen Sheng Wu
  • Biology, Chemistry
    Cancer and Metastasis Reviews
  • 2007
It is suggested that MKPs play an important role not only in the development of cancers, but also in the response of cancer cells to chemotherapy, and their impact on chemotherapy can be exploited for therapeutic benefits.

The ERK cascade

This cascade may serve as a prototype of the other MAPK cascades, and the study of this cascade is likely to contribute to the understanding of mitogenic and other processes in many cell lines and tissues.

The regulation of stress-activated MAP kinase signalling by protein phosphatases

Genetic and biochemical studies in model organisms including yeasts, Drosophila, and C. elegans have provided important insights into the regulation of the stress-responsive JNK and p38 MAPK pathways in mammals, where genetic experiments are beginning to reveal important roles for dual-specificity MKPs in regulating diverse physiological endpoints.

The Expanding Role of p38 Mitogen-Activated Protein Kinase in Programmed Host Cell Death

There is evidence demonstrating that p38 MAPK is a potent trigger of pathogen-induced necrosis driven by mitochondrial membrane disruption and this findings provide an opportunity to repurpose these drugs for improved control of infectious diseases.



Pharmacological inhibitors of MAPK pathways.

The stress-activated protein kinase subfamily of c-Jun kinases

The kinase p54s are the principal c-Jun N-terminal kinases activated by cellular stress and tumour necrosis factor (TNF)-α, hence they are designated stress-activated protein kinases, or SAPKs.

Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human.

All known MAPK module kinases from yeast to humans are defined, what is known about their regulation, defined MAPK substrates, and the function of MAPK in cell physiology are defined.

MAPKK-Independent Activation of p38α Mediated by TAB1-Dependent Autophosphorylation of p38α

The findings suggest that alternative activation pathways contribute to the biological responses of p38α to various stimuli.

Components of a New Human Protein Kinase Signal Transduction Pathway (*)

The MEK5 cDNA was isolated by degenerate PCR and encodes a 444-amino acid protein, which has approximately 40% identity to known MEKs, and ERK5 was identified by a specific interaction with theMEK5 mutants S311A/T315A and K195M in the yeast two-hybrid system.

Extracellular Signal-Regulated Kinase 7 (ERK7), a Novel ERK with a C-Terminal Domain That Regulates Its Activity, Its Cellular Localization, and Cell Growth

Interestingly, the C-terminal tail, not the kinase domain, of ERK7 regulates its nuclear localization and inhibition of growth, and these results elucidate a novel type of MAP kinase whereby interactions via its C- terminal tail, rather than extracellular signal-mediated activation cascades, regulate its activity, localization, and function.

A protein kinase involved in the regulation of inflammatory cytokine biosynthesis

Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds, suggesting that the CSBPs are critical for cytokine production.

c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis.

The novel JNK inhibitor SP600125 completely blocked IL-1--induced accumulation of phospho-Jun and induction of c-Jun transcription in synoviocytes and in joint arthritis, indicating that JNK is an important therapeutic target for RA.

Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway.

It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts, and data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.

Lapadat, ERK Pathway, Science’s STKE (Connections Map, as seen November 2002),; CMP_10705

  • 2002