ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation.

Lechner, Cornelia; Zahalka, Muayad A.; Giot, Jean-François; Møller, Niels; Ullrich, Axel

doi:10.1073/pnas.93.9.4355

Cited by 306 publications

(227 citation statements)

References 25 publications

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“…p38 cDNA was also cloned as a molecule that binds puridinyl imidazole derivatives which are known to inhibit biosynthesis of inflammatory cytokines such as interleukin-1 (IL-1) and tumor-necrosis factor (TNF) in LPS stimulated monocytes [4]. To date, four splice variants of the p38 family have been identified: p38α, p38β [5], p38γ (ERK6, SAPK3) [6,7], and p38δ (SAPK4) [8,9]. Of these, p38 and p38β are ubiquitously expressed while p38γ and p38δ are differentially expressed depending on tissue type.…”

Section: Properties Of P38 Map Kinase Membersmentioning

confidence: 99%

Activation and signaling of the p38 MAP kinase pathway

2005

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The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.

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Section: Properties Of P38 Map Kinase Membersmentioning

confidence: 99%

Activation and signaling of the p38 MAP kinase pathway

2005

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“…This subfamily consists of p38α, p38β, p38γ, and p38δ (158,159). Recent studies have identified p38 MAPK as an important group of signaling molecules that mediate environmental stress responses in various cell types (160,161). In noncardiac cells, p38 MAPK has been implicated in gene expression, morphologic changes, and cell death in response to endotoxin, cytokines, physical stress, and chemical insults (162)(163)(164).…”

Section: Oxidative Stress and Mitogen-activated Protein Kinasesmentioning

confidence: 99%

Molecular and cellular mechanisms of cardiotoxicity.

Kang

2001

Environ Health Perspect

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Cardiotoxicity resulting from detrimental environmental insults has been recognized for a long time. However, extensive studies of the mechanisms involved had not been undertaken until recent years. Advances in molecular biology provide powerful tools and make such studies possible. We are gathering information about cellular events, signaling pathways, and molecular mechanisms of myocardial toxicologic responses to environmental toxicants and pollutants. Severe acute toxic insults cause cardiac cell death instantly. In the early response to mild environmental stimuli, biochemical changes such as alterations in calcium homeostasis occur. These may lead to cardiac arrhythmia, which most often is reversible. Prolonged stimuli activate transcription factors such as activator protein-1 through elevation of intracellular calcium and the subsequent activation of calcineurin. Upregulation by activated transcription factors of hypertrophic genes results in heart hypertrophy, which is a short-term adaptive response to detrimental factors. However, further development of hypertrophy will lead to severe and irreversible cardiomyopathy, and eventually heart failure. From cardiac hypertrophy to heart failure, myocardial cells undergo extensive biochemical and molecular changes. Cardiac hypertrophy causes tissue hypoperfusion, which activates compensatory mechanisms such as production of angiotensin II and norepinephrine. Both further stimulate cardiac hypertrophy and, importantly, activate counterregulatory mechanisms including overexpression of atrial natriuretic peptide and b-type natriuretic peptide, and production of cytokines such as tumor necrosis factor-alpha. This counterregulation leads to myocardial remodeling as well as cell death through apoptosis and necrosis. Cell death through activation of mitochondrial factors and other pathways constitutes an important cellular mechanism of heart failure. Our current knowledge of cardiotoxicity is limited. Further extensive studies are warranted for a comprehensive understanding of this field.

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“…In higher vertebrates, there are four related genes encoding p38␣, p38␤, p38␥, and p38␦ (3)(4)(5)(6)(7)(8)(9)(10)(11). The p38 MAPK proteins exhibit a high degree of structural and functional evolutionary conservation (1,2): the yeast ortholog, Hog1, is also activated in response to osmotic stress, and expression of the human protein in yeast lacking Hog1 restores their ability to grow in high osmolarity media (12).…”

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confidence: 99%

Defining the Involvement of p38α MAPK in the Production of Anti- and Proinflammatory Cytokines Using an SB 203580-resistant Form of the Kinase

Guo

Gerl

Schrader

2003

Journal of Biological Chemistry

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Despite its lack of specificity, the inhibitor SB 203580 has been widely used to implicate p38 mitogen-activated protein kinase (MAPK) in the synthesis of many cytokines. Here we show unequivocally that the production of interleukin (IL)-1␤, IL-6, IL-10, and tumor necrosis factor ␣ (TNF␣) requires p38 MAPK activity by demonstrating that the inhibitory effects of SB 203580 were reversed by expression of an SB 203580-resistant form of p38␣ (SBR-p38␣) that fails to bind to SB 203580. This strategy established the requirement for p38 activity for the lipopolysaccharide-stimulated production of IL-10, IL-1␤, and IL-6 by the monocytic cell WEHI 274 and the production of IL-6 and TNF␣ stimulated by ligation of the Fc-␥ receptor of the mast cell MC/9. Expression of SBR-p38␣ in primary macrophages abrogated the ability of SB 203580 to inhibit the lipopolysaccharide-stimulated production of TNF␣ but not of IL-10. Expression of SBR-p38␣ in primary T lymphocytes abrogated the ability of SB 203580 to inhibit the production of interferon-␥ induced by co-ligation of CD3 and CD28 but not the production of interferon-␥ or IL-10 induced by IL-12. These results suggest that the levels of p38 MAPK activity required for maximal cytokine production vary with different cytokines and stimuli.

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ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation.

Cited by 306 publications

References 25 publications

Activation and signaling of the p38 MAP kinase pathway

Activation and signaling of the p38 MAP kinase pathway

Molecular and cellular mechanisms of cardiotoxicity.

Defining the Involvement of p38α MAPK in the Production of Anti- and Proinflammatory Cytokines Using an SB 203580-resistant Form of the Kinase

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