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 APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway

2011 ◽  
Vol 300 (1) ◽  
pp. E103-E110 ◽  
Author(s):  
Xiaoban Xin ◽  
Lijun Zhou ◽  
Caleb M. Reyes ◽  
Feng Liu ◽  
Lily Q. Dong
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Adaptor Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Scaffolding Protein ◽  
Mapk Activation ◽  
P38 Mapk Pathway ◽  
Mitogen Activated Protein

The adaptor protein APPL1 mediates the stimulatory effect of adiponectin on p38 mitogen-activated protein kinase (MAPK) signaling, yet the underlying mechanism remains unclear. Here we show that, in C2C12 cells, overexpression or suppression of APPL1 enhanced or suppressed, respectively, adiponectin-stimulated p38 MAPK upstream kinase cascade, consisting of transforming growth factor-β-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase 3 (MKK3). In vitro affinity binding and coimmunoprecipitation experiments revealed that TAK1 and MKK3 bind to different regions of APPL1, suggesting that APPL1 functions as a scaffolding protein to facilitate adiponectin-stimulated p38 MAPK activation. Interestingly, suppressing APPL1 had no effect on TNFα-stimulated p38 MAPK phosphorylation in C2C12 myotubes, indicating that the stimulatory effect of APPL1 on p38 MAPK activation is selective. Taken together, our study demonstrated that the TAK1-MKK3 cascade mediates adiponectin signaling and uncovers a scaffolding role of APPL1 in regulating the TAK1-MKK3-p38 MAPK pathway, specifically in response to adiponectin stimulation.

scholarly journals Identification of RAS-Mitogen-Activated Protein Kinase Signaling Pathway Modulators in an ERF1 Redistribution® Screen

2006 ◽  
Vol 11 (4) ◽  
pp. 423-434 ◽  
Author(s):  
Charlotta Grånäs ◽  
Betina Kerstin Lundholt ◽  
Frosty Loechel ◽  
Hans-Christian Pedersen ◽  
Sara Petersen Bjørn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Kinase Inhibitors ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
A Cell ◽  
Protein Kinase Signaling

The RAS-mitogen-activated protein kinase (MAPK) signaling pathway has a central role in regulating the proliferation and survival of both normal and tumor cells. This pathway has been 1 focus area for the development of anticancer drugs, resulting in several compounds, primarily kinase inhibitors, in clinical testing. The authors have undertaken a cell-based, high-throughput screen using a novel ERF1 Redistribution® assay to identify compounds that modulate the signaling pathway. The hit compounds were subsequently tested for activity in a functional cell proliferation assay designed to selectively detect compounds inhibiting the proliferation of MAPK pathway-dependent cancer cells. The authors report the identification of 2 cell membrane-permeable compounds that exhibit activity in the ERF1 Redistribution® assay and selectively inhibit proliferation of MAPK pathway-dependent malignant melanoma cells at similar potencies (IC50 =< 5 μM). These compounds have drug-like structures and are negative in RAF, MEK, and ERK in vitro kinase assays. Drugs belonging to these compound classes may prove useful for treating cancers caused by excessive MAPK pathway signaling. The results also show that cell-based, high-content Redistribution® screens can detect compounds with different modes of action and reveal novel targets in a pathway known to be disease relevant.

scholarly journals Comparative Analysis of Transmembrane Regulators of the Filamentous Growth Mitogen-Activated Protein Kinase Pathway Uncovers Functional and Regulatory Differences

2015 ◽  
Vol 14 (9) ◽  
pp. 868-883 ◽  
Author(s):  
Hema Adhikari ◽  
Lauren M. Caccamise ◽  
Tanaya Pande ◽  
Paul J. Cullen
Keyword(s):  
Protein Kinase ◽  
Mapk Pathway ◽  
Filamentous Growth ◽  
Mapk Signaling ◽  
Fine Tuning ◽  
Mitogen Activated Protein Kinase ◽  
Rate Limiting Step ◽  
Mitogen Activated Protein ◽  
Multiple Signaling ◽  
Growth Pathway

ABSTRACTFilamentous growth is a microbial differentiation response that involves the concerted action of multiple signaling pathways. In budding yeast, one pathway that regulates filamentous growth is a Cdc42p-dependent mitogen-activated protein kinase (MAPK) pathway. Several transmembrane (TM) proteins regulate the filamentous growth pathway, including the signaling mucin Msb2p, the tetraspan osmosensor Sho1p, and an adaptor Opy2p. The TM proteins were compared to identify common and unique features. Msb2p, Sho1p, and Opy2p associated by coimmunoprecipitation analysis but showed predominantly different localization patterns. The different localization patterns of the proteins resulted in part from different rates of turnover from the plasma membrane (PM). In particular, Msb2p (and Opy2p) were turned over rapidly compared to Sho1p. Msb2p signaled from the PM, and its turnover was a rate-limiting step in MAPK signaling. Genetic analysis identified unique phenotypes of cells overexpressing the TM proteins. Therefore, each TM regulator of the filamentous growth pathway has its own regulatory pattern and specific function in regulating filamentous growth. This specialization may be important for fine-tuning and potentially diversifying the filamentation response.

scholarly journals Regulation of PRAK Subcellular Location by p38 MAP Kinases

2003 ◽  
Vol 14 (6) ◽  
pp. 2603-2616 ◽  
Author(s):  
Liguo New ◽  
Yong Jiang ◽  
Jiahuai Han
Keyword(s):  
Protein Kinase ◽  
Nuclear Import ◽  
Nuclear Export ◽  
Map Kinases ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Localization Sequence ◽  
Resting Cells ◽  
Cellular Activation ◽  
Mitogen Activated Protein

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cellular responses to inflammatory stimuli and environmental stress. p38 regulated/activated protein kinase (PRAK, also known as mitogen-activated protein kinase activated protein kinase 5 [MAPKAPK5]) functions downstream of p38α and p38β in mediating the signaling of the p38 pathway. Immunostaining revealed that endogenous PRAK was predominantly localized in the cytoplasm. Interestingly, ectopically expressed PRAK was localized in the nucleus and can be redistributed by coexpression of p38α or p38β to the locations of p38α and p38β. Mutations in the docking groove on p38α/p38β, or the p38-docking site in PRAK, disrupted the PRAK-p38 interaction and impaired the ability of p38α and p38β to redistribute ectopically expressed PRAK, indicating that the location of PRAK could be controlled by its docking interaction with p38α and p38β. Although the majority of PRAK molecules were detected in the cytoplasm, PRAK is consistently shuttling between the cytoplasm and the nucleus. A sequence analysis of PRAK shows that PRAK contains both a putative nuclear export sequence (NES) and a nuclear localization sequence (NLS). The shuttling of PRAK requires NES and NLS motifs in PRAK and can be regulated through cellular activation induced by stress stimuli. The nuclear content of PRAK was reduced after stimulation, which resulted from a decrease in the nuclear import of PRAK and an increase in the nuclear export of PRAK. The nuclear import of PRAK is independent from p38 activation, but the nuclear export requires p38-mediated phosphorylation of PRAK. Thus, the subcellular distribution of PRAK is determined by multiple factors including its own NES and NLS, docking interactions between PRAK and docking proteins, phosphorylation of PRAK, and cellular activation status. The p38 MAPKs not only regulate PRAK activity and PRAK activation-related translocation, but also dock PRAK to selected subcellular locations in resting cells.

Engagement of CD11b and CD11c β2 integrin by antibodies or soluble CD23 induces IL-1β production on primary human monocytes through mitogen-activated protein kinase–dependent pathways

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3868-3877 ◽  
Author(s):  
Roger Rezzonico ◽  
Rachel Chicheportiche ◽  
Veronique Imbert ◽  
Jean-Michel Dayer
Keyword(s):  
Protein Kinase ◽  
Messenger Rna ◽  
Transcriptional Control ◽  
Map Kinases ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Transcriptional Level ◽  
Mitogen Activated Protein ◽  
Dose Dependent Fashion ◽  
Β2 Integrins

β2 integrins are involved in the recruitment of leukocytes to inflammatory sites and in cellular activation. We demonstrate that ligation of CD11b (Mac-1, CR3) or CD11c (p150, CR4) alpha chains of β2 integrins by mAbs or soluble chimeric CD23 (sCD23) on human freshly isolated monocytes rapidly stimulates high levels of interleukin-1β production. This induction takes place at the transcriptional level and is regulated by members of the mitogen-activated protein kinase (MAPK) family. Indeed, stimulation of monocytes through engagement of CD11b or CD11c results in the phosphorylation and activation of ERK1, ERK2, and p38/SAPK2 MAP kinases. U0126, a potent inhibitor of the upstream activator of ERK1/2, ie, MEK1/2, suppresses IL-1β messenger RNA (mRNA) expression in a dose-dependent fashion, showing the implication of this pathway in the transcriptional control of IL-1β production. On the other hand, inhibition of p38 by SB203580 indicates that this MAPK is involved in the control of IL-1β production at both transcriptional and translational levels. Together these data demonstrate that ligation of CD11b and CD11c β2 integrins by mAbs or sCD23 fusion proteins triggers the activation of 2 distinct MAPK signaling pathways that cooperate in controlling IL-1β synthesis at different levels.

Engagement of CD11b and CD11c β2 integrin by antibodies or soluble CD23 induces IL-1β production on primary human monocytes through mitogen-activated protein kinase–dependent pathways

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3868-3877 ◽  
Author(s):  
Roger Rezzonico ◽  
Rachel Chicheportiche ◽  
Veronique Imbert ◽  
Jean-Michel Dayer
Keyword(s):  
Protein Kinase ◽  
Messenger Rna ◽  
Transcriptional Control ◽  
Map Kinases ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Transcriptional Level ◽  
Mitogen Activated Protein ◽  
Dose Dependent Fashion ◽  
Β2 Integrins

Abstract β2 integrins are involved in the recruitment of leukocytes to inflammatory sites and in cellular activation. We demonstrate that ligation of CD11b (Mac-1, CR3) or CD11c (p150, CR4) alpha chains of β2 integrins by mAbs or soluble chimeric CD23 (sCD23) on human freshly isolated monocytes rapidly stimulates high levels of interleukin-1β production. This induction takes place at the transcriptional level and is regulated by members of the mitogen-activated protein kinase (MAPK) family. Indeed, stimulation of monocytes through engagement of CD11b or CD11c results in the phosphorylation and activation of ERK1, ERK2, and p38/SAPK2 MAP kinases. U0126, a potent inhibitor of the upstream activator of ERK1/2, ie, MEK1/2, suppresses IL-1β messenger RNA (mRNA) expression in a dose-dependent fashion, showing the implication of this pathway in the transcriptional control of IL-1β production. On the other hand, inhibition of p38 by SB203580 indicates that this MAPK is involved in the control of IL-1β production at both transcriptional and translational levels. Together these data demonstrate that ligation of CD11b and CD11c β2 integrins by mAbs or sCD23 fusion proteins triggers the activation of 2 distinct MAPK signaling pathways that cooperate in controlling IL-1β synthesis at different levels.

scholarly journals Graded Mitogen-Activated Protein Kinase Activity Precedes Switch-Like c-Fos Induction in Mammalian Cells

2005 ◽  
Vol 25 (11) ◽  
pp. 4676-4682 ◽  
Author(s):  
Jeffrey P. MacKeigan ◽  
Leon O. Murphy ◽  
Christopher A. Dimitri ◽  
John Blenis
Keyword(s):  
Protein Kinase ◽  
Cell Fate ◽  
Oocyte Maturation ◽  
Mammalian Cells ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Cell Fate Decisions ◽  
Graded Response ◽  
Mitogen Activated Protein

ABSTRACT The mitogen-activated protein kinase (MAPK) pathway is an evolutionarily conserved signaling module that controls important cell fate decisions in a variety of physiological contexts. During Xenopus oocyte maturation, the MAPK cascade converts an increasing progesterone stimulus into a switch-like, all-or-nothing response. While the importance of such switch-like behavior is widely discussed in the literature, it is not known whether the MAPK pathway in mammalian cells exhibits a switch-like or graded response. For this study, we used flow cytometry and immunofluorescence to generate single-cell measurements of MAPK signaling in Swiss 3T3 fibroblasts. In contrast to the case in Xenopus oocytes, we found that ERK activation in individual mammalian cells is not ultrasensitive and shows a graded response to changes in agonist concentration. Thus, the conserved MAPK signaling module exhibits different systems-level properties in different cellular contexts. Furthermore, the graded ERK response was converted into a more switch-like behavior at the level of immediate-early gene induction and cell cycle progression. Thus, while MAPK signaling is involved in all-or-nothing cell fate decisions for both Xenopus oocyte maturation and mammalian fibroblast proliferation, the underlying mechanisms responsible for the switch-like nature of the cellular responses are different in these two systems, with the mechanism appearing to lie downstream of the kinase cascade in mammalian fibroblasts.

scholarly journals Rho2 Is a Target of the Farnesyltransferase Cpp1 and Acts Upstream of Pmk1 Mitogen-activated Protein Kinase Signaling in Fission Yeast

2006 ◽  
Vol 17 (12) ◽  
pp. 5028-5037 ◽  
Author(s):  
Yan Ma ◽  
Takayoshi Kuno ◽  
Ayako Kita ◽  
Yuta Asayama ◽  
Reiko Sugiura
Keyword(s):  
Protein Kinase ◽  
Fission Yeast ◽  
Mapk Pathway ◽  
Chloride Ion ◽  
Mapk Signaling ◽  
Small Gtpase ◽  
Mitogen Activated Protein Kinase ◽  
Protein Farnesyltransferase ◽  
Mitogen Activated Protein ◽  
Novel Target

We have previously demonstrated that knockout of the calcineurin gene or inhibition of calcineurin activity by immunosuppressants resulted in hypersensitivity to Cl− in fission yeast. We also demonstrated that knockout of the components of the Pmk1 mitogen-activated protein kinase (MAPK) pathway, such as Pmk1 or Pek1 complemented the hypersensitivity to Cl−. Using this interaction between calcineurin and Pmk1 MAPK, here we developed a genetic screen that aims to identify new regulators of the Pmk1 signaling and isolated vic (viable in the presence of immunosuppressant and chloride ion) mutants. One of the mutants, vic1-1, carried a missense mutation in the cpp1+ gene encoding a β subunit of the protein farnesyltransferase, which caused an amino acid substitution of aspartate 155 of Cpp1 to asparagine (Cpp1D155N). Analysis of the mutant strain revealed that Rho2 is a novel target of Cpp1. Moreover, Cpp1 and Rho2 act upstream of Pck2–Pmk1 MAPK signaling pathway, thereby resulting in the vic phenotype upon their mutations. Interestingly, compared with other substrates of Cpp1, defects of Rho2 function were more phenotypically manifested by the Cpp1D155N mutation. Together, our results demonstrate that Cpp1 is a key component of the Pck2–Pmk1 signaling through the spatial control of the small GTPase Rho2.

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 Proprotein Convertase Subtilisin/Kexin Type 9 Promotes Gastric Cancer Metastasis and Suppresses Apoptosis by Facilitating MAPK Signaling Pathway Through HSP70 Up-Regulation

2021 ◽  
Vol 10 ◽  
Author(s):  
Beili Xu ◽  
Shuyu Li ◽  
Yong Fang ◽  
Yanting Zou ◽  
Dongqiang Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Mapk Pathway ◽  
Serum Levels ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Proprotein Convertase ◽  
Mitogen Activated Protein

ObjectiveTo examine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on gastric cancer (GC) progression and prognosis, and to explore the underlying mechanism.MethodsPCSK9 expression levels in human GC tissues were determined by quantitative real-time PCR, western blotting, and immunohistochemical assay. PCSK9 serum levels were detected by enzyme-linked immunosorbent assay. The relationships of PCSK9 and GC progression and survival were analyzed using the Chi-square test, Kaplan-Meier analysis, and Cox proportional hazards model. The effect of PCSK9 on cell invasion, migration, and apoptosis were determined in human GC cell lines and mouse xenograft model separately using PCSK9 knockdown and overexpression strategies. The PCSK9 interacting molecules, screened by co-immunoprecipitation combined with LC-MS/MS, were identified by immunofluorescence localization and western blotting. Additionally, the mitogen-activated protein kinase (MAPK) pathway was assessed by western blotting.ResultsPCSK9 mRNA and protein levels were significantly elevated in GC tissues compared with the paired normal tissues at our medical center (P &lt; 0.001). Notably, the up-regulation of PCSK9 expression in GC tissues was related to tumor progression and poor survival. GC patients had higher serum levels of PCSK9 than the age-matched healthy controls (P &lt; 0.001); PCSK9 promoted invasive and migratory ability and inhibited apoptosis in GC cells with no apparent affection in cell proliferation. The silencing of PCSK9 reversed these effects, suppressing tumor metastasis in vitro and in vivo. Furthermore, PCSK9 maintained these functions through up-regulating heat shock protein 70 (HSP70), ultimately facilitating the mitogen-activated protein kinase (MAPK) pathway.ConclusionCollectively, our data revealed that high PCSK9 expression levels in GC tissue were correlated with GC progression and poor prognosis and that PCSK9 could promote GC metastasis and suppress apoptosis by facilitating MAPK signaling pathway through HSP70 up-regulation. PCSK9 may represent a novel potential therapeutic target in GC.

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