Hautalterung: Über die Rolle von Fibroblasten-Wachstumsfaktoren

2020 ◽  
Vol 8 (2) ◽  
pp. 65-67
Author(s):  
Andrea Schulz
Keyword(s):  
Map Kinases ◽  
Skin Resistance ◽  
Skin Aging ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Functions ◽  
Molecular Alterations ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Relevant Role ◽  
Dermal Cells

Cutaneous aging is a complex and continuous biological process characterized by cellular and molecular alterations, with progressive reduction of the bodyʼs capacity to maintain the homeostasis, senescence, and/or apoptosis of the dermal cells. Fibroblast growth factors (FGF) have elicited studies to evaluate their role of repair and remodeling of the dermis during the skin anti-aging process, since they are regulatory proteins that mediate important signaling pathways and act on cell regeneration and repair processes. FGF acts primarily through binding to tyrosine kinase receptors through the autophosphorylation of their residues, promoting the phosphorylation of serine, threonine, and tyrosine residues of specific target proteins such as Raf-1, MAPK/Erk kinase, and extracellular signal-regulated kinase-1, which are part of the cascade of MAP kinases (mitogen-activated protein kinase). Then, FGF initiate signaling cascades inside the cell, where each kinase activates the following by phosphorylation, resulting in alterations of cellular functions. In addition, the FGF has a relevant role in anti-aging therapy because it is related to collagen and elastin synthesis activation responsible for skin resistance and elasticity, characteristics that are diminished with skin aging. Thus, the present article aims to review several scientific studies that demonstrated the cell signaling involved with the action of FGF on skin aging.

scholarly journals Extracellular Signal-Regulated Kinases Phosphorylate Mitogen-Activated Protein Kinase Phosphatase 3/DUSP6 at Serines 159 and 197, Two Sites Critical for Its Proteasomal Degradation

2005 ◽  
Vol 25 (2) ◽  
pp. 854-864 ◽  
Author(s):  
Sandrine Marchetti ◽  
Clotilde Gimond ◽  
Jean-Claude Chambard ◽  
Thomas Touboul ◽  
Danièle Roux ◽  
...  
Keyword(s):  
Map Kinases ◽  
Fluorescent Protein ◽  
Proteasomal Degradation ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Double Mutation ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein (MAP) kinase phosphatases (MKPs) are dual-specificity phosphatases that dephosphorylate phosphothreonine and phosphotyrosine residues within MAP kinases. Here, we describe a novel posttranslational mechanism for regulating MKP-3/Pyst1/DUSP6, a member of the MKP family that is highly specific for extracellular signal-regulated kinase 1 and 2 (ERK1/2) inactivation. Using a fibroblast model in which the expression of either MKP-3 or a more stable MKP-3-green fluorescent protein (GFP) chimera was induced by tetracycline, we found that serum induces the phosphorylation of MKP-3 and its subsequent degradation by the proteasome in a MEK1 and MEK2 (MEK1/2)-ERK1/2-dependent manner. In vitro phosphorylation assays using glutathione S-transferase (GST)-MKP-3 fusion proteins indicated that ERK2 could phosphorylate MKP-3 on serines 159 and 197. Tetracycline-inducible cell clones expressing either single or double serine mutants of MKP-3 or MKP-3-GFP confirmed that these two sites are targeted by the MEK1/2-ERK1/2 module in vivo. Double serine mutants of MKP-3 or MKP-3-GFP were more efficiently protected from degradation than single mutants or wild-type MKP-3, indicating that phosphorylation of either serine by ERK1/2 enhances proteasomal degradation of MKP-3. Hence, double mutation caused a threefold increase in the half-life of MKP-3. Finally, we show that the phosphorylation of MKP-3 has no effect on its catalytic activity. Thus, ERK1/2 exert a positive feedback loop on their own activity by promoting the degradation of MKP-3, one of their major inactivators in the cytosol, a situation opposite to that described for the nuclear phosphatase MKP-1.

scholarly journals Impact of ERK5 on the Hallmarks of Cancer

2019 ◽  
Vol 20 (6) ◽  
pp. 1426 ◽  
Author(s):  
Barbara Stecca ◽  
Elisabetta Rovida
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Biological Features ◽  
Promising Strategy ◽  
Biological Responses ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Relevant Role ◽  
Almost All

Extracellular signal-regulated kinase 5 (ERK5) belongs to the mitogen-activated protein kinase (MAPK) family that consists of highly conserved enzymes expressed in all eukaryotic cells and elicits several biological responses, including cell survival, proliferation, migration, and differentiation. In recent years, accumulating lines of evidence point to a relevant role of ERK5 in the onset and progression of several types of cancer. In particular, it has been reported that ERK5 is a key signaling molecule involved in almost all the biological features of cancer cells so that its targeting is emerging as a promising strategy to suppress tumor growth and spreading. Based on that, in this review, we pinpoint the hallmark-specific role of ERK5 in cancer in order to identify biological features that will potentially benefit from ERK5 targeting.

scholarly journals IQGAP1 Is a Scaffold for Mitogen-Activated Protein Kinase Signaling

2005 ◽  
Vol 25 (18) ◽  
pp. 7940-7952 ◽  
Author(s):  
Monideepa Roy ◽  
Zhigang Li ◽  
David B. Sacks
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Signaling ◽  
Cellular Functions ◽  
Molecular Scaffold ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Erk Activity

ABSTRACT IQGAP1 modulates many cellular functions such as cell-cell adhesion, transcription, cytoskeletal architecture, and selected signaling pathways. We previously documented that IQGAP1 binds extracellular signal-regulated kinase (ERK) 2 and regulates growth factor-stimulated ERK activity. Here we show that MEK, the molecule immediately upstream of ERK in the Ras/mitogen-activated protein (MAP) kinase signaling cascade, also interacts directly with IQGAP1. Both MEK1 and MEK2 bound IQGAP1 in vitro and coimmunoprecipitated with IQGAP1. The addition of ERK2 enhanced by fourfold the in vitro interaction of MEK2 with IQGAP1 without altering binding of MEK1. Similarly, ERK1 promoted MEK binding to IQGAP1, but either MEK protein altered the association between IQGAP1 and ERK. Epidermal growth factor (EGF) differentially regulated binding, enhancing MEK1 interaction while reducing MEK2 binding to IQGAP1. In addition, both knockdown and overexpression of IQGAP1 reduced EGF-stimulated activation of MEK and ERK. Analyses with selective IQGAP1 mutant constructs indicated that MEK binding is crucial for IQGAP1 to modulate EGF activation of ERK. Our data strongly suggest that IQGAP1 functions as a molecular scaffold in the Ras/MAP kinase pathway.

The role of scaffold proteins in MEK/ERK signalling

2006 ◽  
Vol 34 (5) ◽  
pp. 833-836 ◽  
Author(s):  
D.B. Sacks
Keyword(s):  
Mammalian Cells ◽  
Phorbol Esters ◽  
Biological Response ◽  
Adaptor Proteins ◽  
Scaffold Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Functions ◽  
Extracellular Signal ◽  
Kinase Suppressor Of Ras ◽  
Mitogen Activated Protein

Signal transduction networks allow cells to recognize and respond to changes in the extracellular environment. All eukaryotic cells have MAPK (mitogen-activated protein kinase) pathways that participate in diverse cellular functions, including differentiation, survival, transformation and movement. Five distinct groups of MAPKs have been characterized in mammals, the most extensively studied of which is the Ras/Raf/MEK [MAPK/ERK (extracellular-signal-regulated kinase) kinase]/ERK cascade. Numerous stimuli, including growth factors and phorbol esters, activate MEK/ERK signalling. How disparate extracellular signals are translated by MEK/ERK into different cellular functions remains obscure. Originally identified in yeast, scaffold proteins are now recognized to contribute to the specificity of MEK/ERK pathways in mammalian cells. These scaffolds include KSR (kinase suppressor of Ras), β-arrestin, MEK partner-1, Sef and IQGAP1. Scaffolds organize multiprotein signalling complexes. This targets MEK/ERK to specific substrates and facilitates communication with other pathways, thereby mediating diverse functions. The adaptor proteins regulate the kinetics, amplitude and localization of MEK/ERK signalling, providing an efficient mechanism that enables an individual extracellular stimulus to promote a specific biological response.

scholarly journals Mitogen-Activated Protein Kinase Phosphorylation in Kidneys of βs Sickle Cell Mice

2000 ◽  
Vol 11 (6) ◽  
pp. 1026-1032
Author(s):  
MILITZA KIROYCHEVA ◽  
FAYYAZ AHMED ◽  
GILLIAN M. ANTHONY ◽  
CSABA SZABO ◽  
GARRY J. SOUTHAN ◽  
...  
Keyword(s):  
Map Kinase ◽  
Sickle Cell ◽  
Map Kinases ◽  
Mitogen Activated Protein Kinase ◽  
Reaction Products ◽  
Tyrosine Residues ◽  
Extracellular Signal ◽  
Map Kinase Phosphatase ◽  
Mitogen Activated Protein ◽  
Stress Signals

Abstract. Previous studies in βs sickle cell mice demonstrated renal immunostaining for nitrotyrosine, which is putative evidence of peroxynitrite (ONOO-) formation. ONOO- is known to nitrate tyrosine residues of various enzymes, thereby interfering with phosphorylation and inactivating them. The present study examined the state of phosphorylation of mitogen-activated protein (MAP) kinase signal transduction enzymes, i.e., p38, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Western blot performed with antibodies directed against specific phosphorylated threonine/tyrosine residues of these enzymes demonstrated reduced phosphorylation of renal p38 and a trend toward reduced phosphorylation of ERK. In contrast, phosphorylation of renal JNK was markedly increased compared with normal mice. The abundance of MAP kinase phosphatase-1 (MKP-1), a key upstream enzyme that modulates phosphorylation of MAP kinases, was not different in βsversus normal mice. To determine whether nitration of tyrosine by ONOO- was responsible for reduced phosphorylation of p38 and ERK, mercaptoethylguanidine (MEG), a compound known to reduce inducible isoform of nitric oxide synthase activity and to scavenge ONOO-, was administered to βs mice for 5 d. MEG was found to restore phosphorylation of p38 and ERK toward normal levels. These observations provide evidence that ONOO- (or closely related reaction products of NO) contributes to dephosphorylation of p38 and ERK, and presumably reduces activity of these enzymes. The increased phosphorylation of JNK, which suggests activation of this signaling pathway by extracellular stress signals, may play a role in apoptosis in the kidneys of these mice. The changes in phosphorylation of MAP kinase pathways found in this study could have important consequences for regulation of nuclear transcription factors, and thus renal function and pathology in sickle cell kidneys.

scholarly journals Selective deficiency in protein kinase C isoenzyme expression and inadequacy in mitogen-activated protein kinase activation in cord blood T cells

2003 ◽  
Vol 370 (2) ◽  
pp. 497-503 ◽  
Author(s):  
Charles S.T. HII ◽  
Maurizio COSTABILE ◽  
George C. MAYNE ◽  
Channing J. DER ◽  
Andrew W. MURRAY ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
Cord Blood ◽  
Map Kinase ◽  
Map Kinases ◽  
Mitogen Activated Protein Kinase ◽  
Biochemical Basis ◽  
Kinase Activation ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

The biochemical basis for the reduced lymphokine production by neonatal T cells compared with adult T cells remains poorly defined. Previous studies have raised the possibility that neonatal T cells could be deficient in their ability to transmit signals via protein kinase (PK) C. We now report that while PKC-dependent activation of the mitogen-activated protein (MAP) kinases, c-Jun N-terminal protein kinase and the extracellular signal-regulated protein kinase (ERK)1/ERK2, was deficient in cord blood T cells compared with adult blood T cells, marked activation of the MAP kinases in cord blood T cells was achieved via PKC-independent means. Consistent with a deficiency in the signalling capability of PKC, cord blood T cells were selectively deficient in the expression of PKCβI, ∊, θ and ζ. Stimulation of cord blood T cells resulted in a time-dependent increase in PKC expression, with increases detectable by 4h. This was accompanied by an enhancement in MAP kinase activation via PKC-dependent means. These novel data suggest that an inadequacy in PKC-MAP kinase signalling may be responsible, at least in part, for the phenotype of cord blood T cells.

scholarly journals Filarial Lymphatic Pathology Reflects Augmented Toll-Like Receptor-Mediated, Mitogen-Activated Protein Kinase-Mediated Proinflammatory Cytokine Production

2011 ◽  
Vol 79 (11) ◽  
pp. 4600-4608 ◽  
Author(s):  
Subash Babu ◽  
R. Anuradha ◽  
N. Pavan Kumar ◽  
P. Jovvian George ◽  
V. Kumaraswami ◽  
...  
Keyword(s):  
Lymphatic Filariasis ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Map Kinases ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Map Kinase Pathways

ABSTRACTLymphatic filariasis can be associated with the development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Toll-like receptors (TLRs) are thought to play a major role in the development of filarial pathology. To elucidate the role of TLRs in the development of lymphatic pathology, we examined cytokine responses to different Toll ligands in patients with chronic lymphatic pathology (CP), infected patients with subclinical pathology (INF), and uninfected, endemic-normal (EN) individuals. TLR2, -7, and -9 ligands induced significantly elevated production of Th1 and other proinflammatory cytokines in CP patients in comparison to both INF and EN patients. TLR adaptor expression was not significantly different among the groups; however, both TLR2 and TLR9 ligands induced significantly higher levels of phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein (MAP) kinases (MAPK) as well as increased activation of NF-κB in CP individuals. Pharmacologic inhibition of both ERK1/2 and p38 MAP kinase pathways resulted in significantly diminished production of proinflammatory cytokines in CP individuals. Our data, therefore, strongly suggest an important role for TLR2- and TLR9-mediated proinflammatory cytokine induction and activation of both the MAPK and NF-κB pathways in the development of pathology in human lymphatic filariasis.

scholarly journals Bromamine T (BAT) Exerts Stronger Anti-Cancer Properties than Taurine (Tau)

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 182
Author(s):  
Stella Baliou ◽  
Maria Goulielmaki ◽  
Petros Ioannou ◽  
Christina Cheimonidi ◽  
Ioannis P. Trougakos ◽  
...  
Keyword(s):  
Cytotoxic Effect ◽  
Human Colon ◽  
Mitogen Activated Protein Kinase ◽  
Mitochondrial Apoptosis ◽  
Therapeutic Modalities ◽  
Cancer Pathogenesis ◽  
Extracellular Signal ◽  
Anti Cancer ◽  
Mitogen Activated Protein

Background: Taurine (Tau) ameliorates cancer pathogenesis. Researchers have focused on the functional properties of bromamine T (BAT), a stable active bromine molecule. Both N-bromotaurine (TauNHBr) and BAT exert potent anti-inflammatory properties, but the landscape remains obscure concerning the anti-cancer effect of BAT. Methods: We used Crystal Violet, colony formation, flow cytometry and Western blot experiments to evaluate the effect of BAT and Tau on the apoptosis and autophagy of cancer cells. Xenograft experiments were used to determine the in vivo cytotoxicity of either agent. Results: We demonstrated that both BAT and Tau inhibited the growth of human colon, breast, cervical and skin cancer cell lines. Among them, BAT exerted the greatest cytotoxic effect on both RKO and MDA-MB-468 cells. In particular, BAT increased the phosphorylation of c-Jun N-terminal kinases (JNK½), p38 mitogen-activated protein kinase (MAPK), and extracellular-signal-regulated kinases (ERK½), thereby inducing mitochondrial apoptosis and autophagy in RKO cells. In contrast, Tau exerted its cytotoxic effect by upregulating JNK½ forms, thus triggering mitochondrial apoptosis in RKO cells. Accordingly, colon cancer growth was impaired in vivo. Conclusions: BAT and Tau exerted their anti-tumor properties through the induction of (i) mitochondrial apoptosis, (ii) the MAPK family, and iii) autophagy, providing novel anti-cancer therapeutic modalities.

scholarly journals Chrysin Inhibits TNFα-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes

2021 ◽  
Vol 22 (9) ◽  
pp. 4350
Author(s):  
Hyunjin Yeo ◽  
Younghan Lee ◽  
Sungshin Ahn ◽  
Euitaek Jung ◽  
Yoongho Lim ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Skin Lesions ◽  
Therapeutic Agents ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Signaling Axis ◽  
Factor Alpha ◽  
Necrosis Factor

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that acts as a critical mediator in the pathogenesis of atopic dermatitis (AD). Various therapeutic agents that prevent TSLP function can efficiently relieve the clinical symptoms of AD. However, the downregulation of TSLP expression by therapeutic agents remains poorly understood. In this study, we investigated the mode of action of chrysin in TSLP suppression in an AD-like inflammatory environment. We observed that the transcription factor early growth response (EGR1) contributed to the tumor necrosis factor alpha (TNFα)-induced transcription of TSLP. Chrysin attenuated TNFα-induced TSLP expression by downregulating EGR1 expression in HaCaT keratinocytes. We also showed that the oral administration of chrysin improved AD-like skin lesions in the ear and neck of BALB/c mice challenged with 2,4-dinitrochlorobenzene. We also showed that chrysin suppressed the expression of EGR1 and TSLP by inhibiting the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 mitogen-activated protein kinase pathways. Collectively, the findings of this study suggest that chrysin improves AD-like skin lesions, at least in part, through the downregulation of the ERK1/2 or JNK1/2-EGR1-TSLP signaling axis in keratinocytes.

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