scholarly journals Interaction between Connexin50 and Mitogen-activated Protein Kinase Signaling in Lens Homeostasis

2009 ◽  
Vol 20 (10) ◽  
pp. 2582-2592 ◽  
Author(s):  
Teresa I. Shakespeare ◽  
Caterina Sellitto ◽  
Leping Li ◽  
Clio Rubinos ◽  
Xiaohua Gong ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signal Transduction Pathways ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Mitogen Activated Protein ◽  
Gap Junctional

Both connexins and signal transduction pathways have been independently shown to play critical roles in lens homeostasis, but little is known about potential cooperation between these two intercellular communication systems. To investigate whether growth factor signaling and gap junctional communication interact during the development of lens homeostasis, we examined the effect of mitogen-activated protein kinase (MAPK) signaling on coupling mediated by specific lens connexins by using a combination of in vitro and in vivo assays. Activation of MAPK signaling pathways significantly increased coupling provided by Cx50, but not Cx46, in paired Xenopus laevis oocytes in vitro, as well as between freshly isolated lens cells in vivo. Constitutively active MAPK signaling caused macrophthalmia, cataract, glucose accumulation, vacuole formation in differentiating fibers, and lens rupture in vivo. The specific removal or replacement of Cx50, but not Cx46, ameliorated all five pathological conditions in transgenic mice. These results indicate that MAPK signaling specifically modulates coupling mediated by Cx50 and that gap junctional communication and signal transduction pathways may interact in osmotic regulation during postnatal fiber development.

scholarly journals v-Src phosphorylation of connexin 43 on Tyr247 and Tyr265 disrupts gap junctional communication

2001 ◽  
Vol 154 (4) ◽  
pp. 815-828 ◽  
Author(s):  
Rui Lin ◽  
Bonnie J. Warn-Cramer ◽  
Wendy E. Kurata ◽  
Alan F. Lau
Keyword(s):  
Mammalian Cells ◽  
Connexin 43 ◽  
Experimental System ◽  
Mouse Cell ◽  
Mitogen Activated Protein Kinase ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Gap Junctional

The mechanism by which v-Src disrupts connexin (Cx)43 intercellular gap junctional communication (GJC) is not clear. In this study, we determined that Tyr247 (Y247) and the previously identified Tyr265 (Y265) site of Cx43 were the primary phosphorylation targets for activated Src in vitro. We established an in vivo experimental system by stably expressing v-Src and wild-type (wt) Cx43, or Y247F, Y265F, or Y247F/Y265F Cx43 mutants in a Cx43 knockout mouse cell line. Wt and mutant Cx43 localized to the plasma membrane in the absence or presence of v-Src. When coexpressed with v-Src, the Y247F, Y265F, and Y247F/Y265F Cx43 mutants exhibited significantly reduced levels of tyrosine phosphorylation compared with wt Cx43, indicating that Y247 and Y265 were phosphorylation targets of v-Src in vivo. Most importantly, GJC established by the Y247F, Y265F, and Y247F/Y265F Cx43 mutants was resistant to disruption by v-Src. Furthermore, we did not find evidence for a role for mitogen-activated protein kinase in mediating the disruption of GJC by v-Src. We conclude that phosphorylation on Y247 and Y265 of Cx43 is responsible for disrupting GJC in these mammalian cells expressing v-Src.

scholarly journals Epidermal growth factor stimulates the disruption of gap junctional communication and connexin43 phosphorylation independent of 12-0-tetradecanoylphorbol 13-acetate-sensitive protein kinase C: the possible involvement of mitogen-activated protein kinase.

1993 ◽  
Vol 4 (8) ◽  
pp. 837-848 ◽  
Author(s):  
M Y Kanemitsu ◽  
A F Lau
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Mitogen Activated Protein ◽  
Epidermal Growth ◽  
Phosphopeptide Mapping ◽  
Gap Junctional

We previously reported that epidermal growth factor (EGF) induced the disruption of gap junctional communication (gjc) and serine phosphorylation of connexin43 (Cx43) in T51B rat liver epithelial cells. However, the cascade of events linking EGF receptor activation to these particular responses have not been fully characterized. Furthermore, the serine kinase(s) acting directly on Cx43 remain unidentified. In the current study, we demonstrate that downmodulation of 12-0-tetradecanoylphorbol 13-acetate (TPA)-sensitive protein kinase C (PKC) activity does not affect EGF's ability to reduce junctional permeability or phosphorylate Cx43 in T51B cells. EGF in the presence or absence of chronic TPA treatment stimulated marked increases in Cx43 phosphorylation on numerous sites as determined by two-dimensional tryptic phosphopeptide mapping. Computer-assisted sequence analysis of Cx43 identified several protein kinase phosphorylation consensus sites including two sites for mitogen-activated protein (MAP) kinase. EGF stimulated activation of MAP kinase in a time- and dose-dependent manner where the kinetics of kinase activity corroborated its possible involvement in mediating EGF's effects. Moreover, purified MAP kinase directly phosphorylated Cx43 on serine residues in vitro. Two-dimensional tryptic and chymotryptic phosphopeptide mapping demonstrated that the in vitro phosphopeptides represented a specific subset of the in vivo phosphopeptides produced in response to EGF after chronic TPA treatment. Therefore, EGF-induced disruption of gjc and phosphorylation of Cx43 may be mediated in part by MAP kinase in vivo.

scholarly journals Role for the Ran Binding Protein, Mog1p, in Saccharomyces cerevisiae SLN1-SKN7 Signal Transduction

2004 ◽  
Vol 3 (6) ◽  
pp. 1544-1556 ◽  
Author(s):  
Jade Mei-Yeh Lu ◽  
Robert J. Deschenes ◽  
Jan S. Fassler
Keyword(s):  
Signal Transduction ◽  
Transcription Factor ◽  
Osmotic Stress ◽  
Kinase Activity ◽  
Mitogen Activated Protein Kinase ◽  
Osmotic Response ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

ABSTRACT Yeast Sln1p is an osmotic stress sensor with histidine kinase activity. Modulation of Sln1 kinase activity in response to changes in the osmotic environment regulates the activity of the osmotic response mitogen-activated protein kinase pathway and the activity of the Skn7p transcription factor, both important for adaptation to changing osmotic stress conditions. Many aspects of Sln1 function, such as how kinase activity is regulated to allow a rapid response to the continually changing osmotic environment, are not understood. To gain insight into Sln1p function, we conducted a two-hybrid screen to identify interactors. Mog1p, a protein that interacts with the yeast Ran1 homolog, Gsp1p, was identified in this screen. The interaction with Mog1p was characterized in vitro, and its importance was assessed in vivo. mog1 mutants exhibit defects in SLN1-SKN7 signal transduction and mislocalization of the Skn7p transcription factor. The requirement for Mog1p in normal localization of Skn7p to the nucleus does not fully account for the mog1-related defects in SLN1-SKN7 signal transduction, raising the possibility that Mog1p may play a role in Skn7 binding and activation of osmotic response genes.

scholarly journals MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model

2021 ◽  
Author(s):  
William E. Tidyman ◽  
Alice F. Goodwin ◽  
Yoshiko Maeda ◽  
Ophir D. Klein ◽  
Katherine A. Rauen
Keyword(s):  
Mouse Model ◽  
Mapk Pathway ◽  
Mek Inhibitor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Costello Syndrome ◽  
Skeletal Myopathy ◽  
Mitogen Activated Protein

Costello syndrome (CS) is a congenital disorder caused by heterozygous activating germline HRAS mutations in the canonical Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. CS is one of the RASopathies, a large group of syndromes due to mutations within various components of the Ras/MAPK pathway. An important part of the phenotype that greatly impacts quality of life is hypotonia. To gain a better understanding of the mechanisms underlying hypotonia in CS, a mouse model with an activating HrasG12V allele was utilized. We identified a skeletal myopathy that was due in part to an inhibition of embryonic myogenesis and myofiber formation, resulting in a reduction of myofiber size and number that led to reduced muscle mass and strength. In addition to hyperactivation of the Ras/MAPK and PI3K/AKT pathways, there was a significant reduction of p38 signaling, as well as global transcriptional alterations consistent with the myopathic phenotype. Inhibition of Ras/MAPK pathway signaling using a MEK inhibitor rescued the HrasG12V myopathy phenotype both in vitro and in vivo, demonstrating that increased MAPK signaling is the main cause of the muscle phenotype in CS.

Synthesis of Baicalein Modified Cerium Oxide Nanoparticles for Inhibitory Activation of NF-κB and Mitogen-Activated Protein Kinase Signals in Rotenone-Induced Parkinsonian Rats

2020 ◽  
Vol 12 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Zhuang Zhang ◽  
Meng Zhong ◽  
Jun Wang ◽  
Dongjian Xia ◽  
Jinsuo Bao
Keyword(s):  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Cytokine Release ◽  
Motor Impairments ◽  
Synthetic Procedure ◽  
Mitogen Activated Protein ◽  
Neuroprotective Efficacy ◽  
Experimental Findings

Baicalein is one of the chief flavones extracted from Scutellariabaicalensis georgi which was earlier reported for its neuroprotective efficacy against Parkinson's disease (PD). In the present study, a simple and efficient synthetic procedure for the preparation of CeO2NPs using Ce(NO3)3 as a primary precursor and baicalein as a stabilizing agent was proposed. Further, the neuroprotective response of baicalein stabilized CeO2 NPs against rotenone-stimulated parkinsonian diseased mice has been explored both in-vitro and in-vivo. From the experimental findings, it was also evident that baicalein exposure has enhanced the motor impairments, and hindered the pro-inflammatory cytokine release and blocked the NF-κB along with MAPK signaling pathway in rotenone-stimulated PD rat models.

scholarly journals In Vivo and In Vitro Study of Immunostimulation by Leuconostoc lactis-Produced Gluco-Oligosaccharides

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3994 ◽  
Author(s):  
Sulhee Lee ◽  
In Ho Song ◽  
Young-Seo Park
Keyword(s):  
In Vitro Study ◽  
Treated Group ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Raw264.7 Macrophages ◽  
Donor And Acceptor ◽  
Mitogen Activated Protein ◽  
Leuconostoc Lactis

Glycosyltransferase-producing Leuconostoc lactis CCK940 produces CCK- oligosaccharides, gluco-oligosaccharide molecules, using sucrose and maltose as donor and acceptor molecules, respectively. In this study, the immunostimulatory activities of CCK-oligosaccharides on RAW264.7 macrophages and BALB/c mice were evaluated. CCK-oligosaccharides induced the expression of phosphorylated-p38, extracellular-signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) and upregulation of phagocytic activity in RAW264.7 macrophages, suggesting their involvement in mitogen-activated protein kinase (MAPK) signaling pathway and phagocytosis. When CCK-oligosaccharides were administered to mice intraperitoneally injected with cyclophosphamide (CY), spleen indices and expressions of interleukin (IL)-6, IL–10, and tumor necrosis factor-α increased, compared with those in only CY-treated group. These findings suggest that CCK-oligosaccharides can be used as an effective immunostimulating agent.

scholarly journals Role of Muramyl Dipeptide in Lipopolysaccharide-Mediated Biological Activity and Osteoclast Activity

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Hideki Kitaura ◽  
Masahiko Ishida ◽  
Keisuke Kimura ◽  
Haruki Sugisawa ◽  
Akiko Kishikawa ◽  
...  
Keyword(s):  
Biological Activities ◽  
Muramyl Dipeptide ◽  
Mapk Signaling ◽  
Osteoclast Formation ◽  
Mitogen Activated Protein Kinase ◽  
Immunological Activity ◽  
Mitogen Activated Protein

Lipopolysaccharide (LPS) is an endotoxin and bacterial cell wall component that is capable of inducing inflammation and immunological activity. Muramyl dipeptide (MDP), the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is another inflammation-inducing molecule that is ubiquitously expressed by bacteria. Several studies have shown that inflammation-related biological activities were synergistically induced by interactions between LPS and MDP. MDP synergistically enhances production of proinflammatory cytokines that are induced by LPS exposure. Injection of MDP induces lethal shock in mice challenged with LPS. LPS also induces osteoclast formation and pathological bone resorption; MDP enhances LPS induction of both processes. Furthermore, MDP enhances the LPS-induced receptor activator of NF-κB ligand (RANKL) expression and toll-like receptor 4 (TLR4) expression bothin vivoandin vitro. Additionally, MDP enhances LPS-induced mitogen-activated protein kinase (MAPK) signaling in stromal cells. Taken together, these findings suggest that MDP plays an important role in LPS-induced biological activities. This review discusses the role of MDP in LPS-mediated biological activities, primarily in relation to osteoclastogenesis.

Complexity and Modularity of MAPK Signaling Networks

2013 ◽  
pp. 676-689
Author(s):  
George V. Popescu ◽  
Sorina C. Popescu
Keyword(s):  
Large Scale ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Networks ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Computational Modeling And Simulation ◽  
Definition Of

Signaling through mitogen-activated protein kinase (MAPK) cascades is a conserved and fundamental process in all eukaryotes. This chapter reviews recent progress made in the identification of components of MAPK signaling networks using novel large scale experimental methods. It also presents recent landmarks in the computational modeling and simulation of the dynamics of MAPK signaling modules. The in vitro MAPK signaling network reconstructed from predicted phosphorylation events is dense, supporting the hypothesis of a combinatorial control of transcription through selective phosphorylation of sets of transcription factors. Despite the fact that additional co-factors and scaffold proteins may regulate the dynamics of signal transduction in vivo, the complexity of MAPK signaling networks supports a new model that departs significantly from that of the classical definition of a MAPK cascade.

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