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

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Pulak R. Manna ◽  
Douglas M. Stocco
Keyword(s):  
Protein Kinase ◽  
Regulatory Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascades ◽  
Steroid Synthesis ◽  
Mapk Kinase ◽  
Mapk Cascades ◽  
Steroidogenic Cell ◽  
Mitogen Activated Protein

Mitogen-activated protein kinases (MAPKs) comprise a family of serine/threonine kinases that are activated by a large variety of extracellular stimuli and play integral roles in controlling many cellular processes, from the cell surface to the nucleus. The MAPK family includes four distinct MAPK cascades, that is, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, c-Jun N-terminal kinase or stress-activated protein kinase, and ERK5. These MAPKs are essentially operated through three-tiered consecutive phosphorylation events catalyzed by a MAPK kinase kinase, a MAPK kinase, and a MAPK. MAPKs lie in protein kinase cascades. The MAPK signaling pathways have been demonstrated to be associated with events regulating the expression of the steroidogenic acute regulatory protein (StAR) and steroidogenesis in steroidogenic tissues. However, it has become clear that the regulation of MAPK-dependent StAR expression and steroid synthesis is a complex process and is context dependent. This paper summarizes 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.

scholarly journals Mating and Pathogenic Development of the Smut Fungus Ustilago maydis Are Regulated by One Mitogen-Activated Protein Kinase Cascade

2003 ◽  
Vol 2 (6) ◽  
pp. 1187-1199 ◽  
Author(s):  
Philip Müller ◽  
Gerhard Weinzierl ◽  
Andreas Brachmann ◽  
Michael Feldbrügge ◽  
Regine Kahmann
Keyword(s):  
Protein Kinase ◽  
Ustilago Maydis ◽  
Mapk Signaling ◽  
Tube Formation ◽  
Mitogen Activated Protein Kinase ◽  
Phytopathogenic Fungus ◽  
Mapk Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

ABSTRACT In the phytopathogenic fungus Ustilago maydis, pheromone-mediated cell fusion is a prerequisite for the generation of the infectious dikaryon. The pheromone signal elevates transcription of the pheromone genes and elicits formation of conjugation hyphae. Cyclic AMP and mitogen-activated protein kinase (MAPK) signaling are involved in this process. The MAPK cascade is presumed to be composed of Ubc4 (MAPK kinase kinase), Fuz7 (MAPK kinase), and Ubc3/Kpp2 (MAPK). We isolated the kpp4 gene and found it to be allelic to ubc4. Epistasis analyses with constitutively active alleles of kpp4 and fuz7 substantiate that Kpp4, Fuz7, and Kpp2/Ubc3 are components of the same module. Moreover, we demonstrate that Fuz7 activates Kpp2 and shows interactions in vitro. Signaling via this cascade regulates expression of pheromone-responsive genes, presumably through acting on the transcription factor Prf1. Interestingly, the same cascade is needed for conjugation tube formation, and this process does not involve Prf1. In addition, fuz7 as well as kpp4 deletion strains are nonpathogenic, while kpp2 deletion mutants are only attenuated in pathogenesis. Here we show that strains expressing the unphosphorylatable allele kpp2T182A/Y184F are severely affected in tumor induction and display defects in early infection-related differentiation.

scholarly journals KSR1 Modulates the Sensitivity of Mitogen-Activated Protein Kinase Pathway Activation in T Cells without Altering Fundamental System Outputs

2009 ◽  
Vol 29 (8) ◽  
pp. 2082-2091 ◽  
Author(s):  
Joseph Lin ◽  
Angus Harding ◽  
Emanuele Giurisato ◽  
Andrey S. Shaw
Keyword(s):  
T Cells ◽  
T Cell ◽  
Protein Kinase ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Activation ◽  
Cell Fate Decisions ◽  
Mapk Cascades ◽  
Wide Range ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein kinase (MAPK) cascades are evolutionarily conserved signaling pathways that regulate cell fate decisions. They generate a wide range of signal outputs, including graded and digital responses. In T cells, MAPK activation is digital in response to T-cell-receptor stimulation; however, whether other receptors on T cells that lead to MAPK activation are graded or digital is unknown. Here we evaluate MAPK activation in T cells at the single-cell level. We show that T cells responded digitally to stimulation with superantigen-loaded antigen-presenting cells, whereas they responded in a graded manner to the chemokine SDF-1, demonstrating that the system output of the MAPK module is highly plastic and determined by components upstream of the MAPK module. These findings also confirm that different MAPK system outputs are used by T cells to control discrete biological functions. Scaffold proteins are essential for proper MAPK signaling and function as they physically assemble multiple components and regulators of MAPK cascades. We found that the scaffold protein KSR1 regulated the threshold required for MAPK activation in T cells without affecting the nature of the response. We conclude that KSR1 plays a central role in determining the sensitivity of T-cell responses and is thus well positioned as a key control point.

scholarly journals The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling

2016 ◽  
Vol 90 (21) ◽  
pp. 9743-9757 ◽  
Author(s):  
Finny S. Varghese ◽  
Bastian Thaa ◽  
Siti Naqiah Amrun ◽  
Diane Simarmata ◽  
Kai Rausalu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Chikungunya Virus ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascades ◽  
Mitogen Activated Protein ◽  
Protein Kinase Signaling ◽  
Mapk Signaling Pathways

ABSTRACT Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the last decade. We recently identified the nontoxic plant alkaloid berberine as an antiviral substance against CHIKV in a high-throughput screen. Here, we show that berberine is effective in multiple cell types against a variety of CHIKV strains, also at a high multiplicity of infection, consolidating the potential of berberine as an antiviral drug. We excluded any effect of this compound on virus entry or on the activity of the viral replicase. A human phosphokinase array revealed that CHIKV infection specifically activated the major mitogen-activated protein kinase (MAPK) signaling pathways extracellular signal-related kinase (ERK), p38 and c-Jun NH 2 -terminal kinase (JNK). Upon treatment with berberine, this virus-induced MAPK activation was markedly reduced. Subsequent analyses with specific inhibitors of these kinases indicated that the ERK and JNK signaling cascades are important for the generation of progeny virions. In contrast to specific MAPK inhibitors, berberine lowered virus-induced activation of all major MAPK pathways and resulted in a stronger reduction in viral titers. Further, we assessed the in vivo efficacy of berberine in a mouse model and measured a significant reduction of CHIKV-induced inflammatory disease. In summary, we demonstrate the efficacy of berberine as a drug against CHIKV and highlight the importance of the MAPK signaling pathways in the alphavirus infectious cycle. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne virus that causes severe and persistent muscle and joint pain and has recently spread to the Americas. No licensed drug exists to counter this virus. In this study, we report that the alkaloid berberine is antiviral against different CHIKV strains and in multiple human cell lines. We demonstrate that berberine collectively reduced the virus-induced activation of cellular mitogen-activated protein kinase signaling. The relevance of these signaling cascades in the viral life cycle was emphasized by specific inhibitors of these kinase pathways, which decreased the production of progeny virions. Berberine significantly reduced CHIKV-induced inflammatory disease in a mouse model, demonstrating efficacy of the drug in vivo . Overall, this work makes a strong case for pursuing berberine as a potential anti-CHIKV therapeutic compound and for exploring the MAPK signaling pathways as antiviral targets against alphavirus infections.

scholarly journals Mitogen-Activated Protein Kinase Cascade Required for Regulation of Development and Secondary Metabolism in Neurospora crassa

2008 ◽  
Vol 7 (12) ◽  
pp. 2113-2122 ◽  
Author(s):  
Gyungsoon Park ◽  
Songqin Pan ◽  
Katherine A. Borkovich
Keyword(s):  
Protein Kinase ◽  
Neurospora Crassa ◽  
Secondary Metabolism ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascades ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Sexual Cross ◽  
Dopa Melanin

ABSTRACT Mitogen-activated protein kinase (MAPK) signaling cascades are composed of MAPK kinase kinases (MAPKKKs), MAPK kinases (MAPKKs), and MAPKs. In this study, we characterize components of a MAPK cascade in Neurospora crassa (mik-1, MAPKKK; mek-1, MAPKK; and mak-1, MAPK) homologous to that controlling cell wall integrity in Saccharomyces cerevisiae. Growth of basal hyphae is significantly reduced in mik-1, mek-1, and mak-1 deletion mutants on solid medium. All three mutants formed short aerial hyphae and the formation of asexual macroconidia was reduced in Δmik-1 mutants and almost abolished in Δmek-1 and Δmak-1 strains. In contrast, the normally rare asexual spores, arthroconidia, were abundant in cultures of the three mutants. Δmik-1, Δmek-1, and Δmak-1 mutants were unable to form protoperithecia or perithecia when used as females in a sexual cross. The MAK-1 MAPK was not phosphorylated in Δmik-1 and Δmek-1 mutants, consistent with the involvement of MIK-1, MEK-1, and MAK-1 in the same signaling cascade. Interestingly, we observed increased levels of mRNA and protein for tyrosinase in the mutants under nitrogen starvation, a condition favoring sexual differentiation. Tyrosinase is an enzyme that catalyzes production of the secondary metabolite l-DOPA melanin. These results implicate the MAK-1 pathway in regulation of development and secondary metabolism in filamentous fungi.

scholarly journals Selective Regulation of c-jun Gene Expression by Mitogen-Activated Protein Kinases via the 12-O-Tetradecanoylphorbol-13-Acetate- Responsive Element and Myocyte Enhancer Factor 2 Binding Sites

2005 ◽  
Vol 25 (9) ◽  
pp. 3784-3792 ◽  
Author(s):  
Midori Kayahara ◽  
Xin Wang ◽  
Cathy Tournier
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cell Fate ◽  
P38 Mapk ◽  
Physiological Role ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Cascades ◽  
Mitogen Activated Protein

ABSTRACT To further understand how the mitogen-activated protein kinase (MAPK) signaling pathways regulate AP-1 activity, we have elucidated the physiological role of these cascades in the regulation of c-jun gene expression. c-Jun is a crucial component of AP-1 complexes and has been shown in vitro to be a point of integration of numerous signals that can differentially affect its expression as well as its transcriptional activity. Our strategy was based on the use of (i) genetically modified fibroblasts deficient in components of the MAPK cascades and (ii) pharmacological reagents. The results demonstrate that c-Jun NH2-terminal protein kinase (JNK) is essential for a basal level of c-Jun expression and for c-Jun phosphorylation in response to stress. In addition to JNK, p38 MAPK or ERK1/2 and ERK5 are required for mediating UV radiation- or epidermal growth factor (EGF)-induced c-Jun expression, respectively. Further studies indicate that p38 MAPK inhibits the activation of JNK in response to EGF, causing a down-regulation of c-Jun. Overall, these data provide important insights into the mechanisms that ultimately determine the function of c-Jun as a regulator of cell fate.

scholarly journals MITOGEN ACTIVATED PROTEIN KINASE: FUNCTION AND RESPONSES TO DIFFERENT STRESSES IN PLANTS

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Sara Khan ◽  
Nadia Iqbal ◽  
Farah Deeba ◽  
Raheela Jabeen
Keyword(s):  
Protein Kinase ◽  
Map Kinases ◽  
Mapk Pathway ◽  
Ultra Violet ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Ultra Violet Radiation ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Regulation Functions

Mitogen Activated Protein Kinase (MAPK) pathway is the most commonly studied signaling mechanisms, consisting of different groups of protein kinases that participate in regularly connecting interpretation of external stimuli that can change in gene expression or cellular organization within eukaryotic systems. The MAP kinase pathways functions in plants cell signaling (intra- and extra). MAPK cascades follow a response system. MAP kinases are the component of kinase constituents that deliver signals from sensors to responders in eukaryotes including plants. Several pathways are activated under different environmental stresses. Stimulating agents may be biological (biotic) like microbial infections or environmental (abiotic) like temperatures threshold, high salt concentration, drought, heavy metal, Ultra-violet radiation, ozone gases and reactive oxygen species (ROS). The involvement of MAPK signaling pathway in different stresses has been widely studied. In this review we also try to highlight MAPK cascades, its regulation, functions and recent findings in various cellular processes against stress conditions.

scholarly journals Topical Spilanthol Inhibits MAPK Signaling and Ameliorates Allergic Inflammation in DNCB-Induced Atopic Dermatitis in Mice

2019 ◽  
Vol 20 (10) ◽  
pp. 2490 ◽  
Author(s):  
Wen-Chung Huang ◽  
Chun-Hsun Huang ◽  
Sindy Hu ◽  
Hui-Ling Peng ◽  
Shu-Ju Wu
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Protein Kinase ◽  
Allergic Inflammation ◽  
Skin Lesions ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Pathways ◽  
Mitogen Activated Protein ◽  
Cox 2

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.

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