scholarly journals Docking sites on mitogen-activated protein kinase (MAPK) kinases, MAPK phosphatases and the Elk-1 transcription factor compete for MAPK binding and are crucial for enzymic activity

2003 ◽  
Vol 370 (3) ◽  
pp. 1077-1085 ◽  
Author(s):  
A. Jane BARDWELL ◽  
Mahsa ABDOLLAHI ◽  
Lee BARDWELL
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Protein Interactions ◽  
Expression Patterns ◽  
Enzymic Activity ◽  
Mitogen Activated Protein Kinase ◽  
Docking Site ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Docking Sites

Mitogen-activated protein kinase (MAPK) cascades control gene expression patterns in response to extracellular stimuli. MAPK/ERK (extracellular-signal-regulated kinase) kinases (MEKs) activate MAPKs by phosphorylating them; activated MAPKs, in turn, phosphorylate target transcription factors, and are deactivated by phosphatases. One mechanism for maintaining signal specificity and efficiency is the interaction of MAPKs with their substrates and regulators through high-affinity docking sites. In the present study, we show that peptides corresponding to the MAPK-docking sites of MEK1, MEK2, Ste7, Elk-1 and MAPK phosphatase (MKP)-2 potently inhibit MEK2 phosphorylation of ERK2, ERK2 phosphorylation of Elk-1, and MKP-1 dephosphorylation of ERK2. Each peptide inhibited multiple reactions; for example, the MEK2 peptide inhibited not only MEK2, but also ERK2 and MKP-1. In addition, these docking-site peptides inhibited MEK2—ERK2 binding. The MAPK-docking site of MEK1 also potently stimulated ERK2-mediated phosphorylation of a target site on the same peptide. Control peptides with mutations of conserved basic and hydrophobic residues of the MAPK-docking site consensus lacked biological activity. We conclude that MEKs, MKPs and the Elk-1 transcription factor compete for binding to the same region of ERK2 via protein—protein interactions that are crucial for kinase/phosphatase activity.

scholarly journals Comprehensive analysis of mitogen-activated protein kinase cascades in chrysanthemum

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5037 ◽  
Author(s):  
Aiping Song ◽  
Yueheng Hu ◽  
Lian Ding ◽  
Xue Zhang ◽  
Peiling Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Expression Patterns ◽  
Defense Responses ◽  
Mitogen Activated Protein Kinase ◽  
Pcr Analysis ◽  
Yeast Two Hybrid ◽  
Qrt Pcr ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Two Hybrid

Background Mitogen-activated protein kinase (MAPK) cascades, an important type of pathway in eukaryotic signaling networks, play a key role in plant defense responses, growth and development. Methods Phylogenetic analysis and conserved motif analysis of the MKK and MPK families in Arabidopsis thaliana, Helianthus annuus and Chrysanthemum morifolium classified MKK genes and MPK genes. qRT-PCR was used for the expression patterns of CmMPK and CmMKK genes, and yeast two-hybrid assay was applied to clear the interaction between CmMPKs and CmMKKs. Results We characterized six MKK genes and 11 MPK genes in chrysanthemum based on transcriptomic sequences and classified these genes into four groups. qRT-PCR analysis demonstrated that CmMKKs and CmMPKs exhibited various expression patterns in different organs of chrysanthemum and in response to abiotic stresses and phytohormone treatments. Furthermore, a yeast two-hybrid assay was applied to analyze the interaction between CmMKKs and CmMPKs and reveal the MAPK cascades in chrysanthemum. Discussion Our data led us to propose that CmMKK4-CmMPK13 and CmMKK2-CmMPK4 may be involved in regulating salt resistance and in the relationship between CmMKK9 and CmMPK6 and temperature stress.

scholarly journals Activation of a Novel Transcription Factor through Phosphorylation by WIPK, a Wound-Induced Mitogen-Activated Protein Kinase in Tobacco Plants

2005 ◽  
Vol 139 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Yun-Kiam Yap ◽  
Yutaka Kodama ◽  
Frank Waller ◽  
Kwi Mi Chung ◽  
Hirokazu Ueda ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Tobacco Plants ◽  
Mitogen Activated Protein

scholarly journals Exercise-induced mitogen-activated protein kinase signalling in skeletal muscle

2004 ◽  
Vol 63 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Yun Chau Long ◽  
Ulrika Widegren ◽  
Juleen R. Zierath
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Muscle Contraction ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Cascades ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Exercise Induced ◽  
Response To Exercise

Exercise training improves glucose homeostasis through enhanced insulin sensitivity in skeletal muscle. Muscle contraction through physical exercise is a physiological stimulus that elicits multiple biochemical and biophysical responses and therefore requires an appropriate control network. Mitogen-activated protein kinase (MAPK) signalling pathways constitute a network of phosphorylation cascades that link cellular stress to changes in transcriptional activity. MAPK cascades are divided into four major subfamilies, including extracellular signal-regulated kinases 1 and 2, p38 MAPK, c-Jun NH2-terminal kinase and extracellular signal-regulated kinase 5. The present review will present the current understanding of parallel MAPK signalling in human skeletal muscle in response to exercise and muscle contraction, with an emphasis on identifying potential signalling mechanisms responsible for changes in gene expression.

scholarly journals Genome-wide identification of MAPKKK genes and their response to phytoplasma stress in Chinese jujube (Ziziphus jujuba Mill.)

2019 ◽  
Author(s):  
ZhiGuo Liu ◽  
Lixin Wang ◽  
Chaoling Xue ◽  
Yuetong Chu ◽  
Weilin Gao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Expression Profiles ◽  
Duplication Event ◽  
Kinase Domain ◽  
Mitogen Activated Protein Kinase ◽  
Chinese Jujube ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Phytoplasma Infection ◽  
Gene Structures

Abstract Backgrounds Mitogen activated protein kinase (MAPK) cascades play vital roles in signal transduction in response to various biotic and abiotic stresses. In the previous study we have identified 10 ZjMAPKs and 5 ZjMAPKKs in Chinese jujube genome and found some crucial members of ZjMAPKs and ZjMAPKKs might function importantly in the process of phytoplasma infection. But how these ZjMAPKKs were modulated by ZjMAPKKKs during this process is still elusive and little information is known about the MAPKKKs in Chinese jujube. Results In the current study, 56 ZjMAPKKKs were identified in the jujube genome and all of them contain the key S-TKc (serine/threonine protein kinase) domain which distributed in all 12 chromosomes. Phylogenetic analysis showed that these ZjMAPKKKs could be classified into two subfamilies, of which 41 belonged to Raf, and 15 to MEKK subfamily. In addition, the ZjMAPKKKs in each subfamily share the same conserved motifs and gene structures, one pair of ZjMAPKKKs (15/16) was the only tandem duplication event on Chromosome 5. Furthermore, the expression profiles of these MAPKKKs in response to phytoplasma disease were investigated by qPCR. In the three main infected tissues (witches’ broom leaves, phyllody leaves, apparent normal leaves), the ZjMAPKKK26 and 45 were significantly up regulated and the ZjMAPKKK3, 43 and 50 were down regulated. While the ZjMAPKKK4, 10, 25 and 44 were significant highly induced in the sterile cultivated tissues infected by phytoplasma, and the ZjMAPKKK7, 30, 35, 37, 40, 41, 43 and 46 were significantly down regulated. Conclusions The identification and classification analysis of ZjMAPKKKs was firstly reported and some key individual ZjMAPKKKs genes might play essential roles in response to phytoplasma infection. This could provide initial understanding for the mechanism that how the ZjMAPKKKs were involved in jujube - phytoplasma infection.

scholarly journals MicroRNA-132 Plays an Independent Prognostic Role in Pancreatic Ductal Adenocarcinoma and Acts as a Tumor Suppressor

2019 ◽  
Vol 18 ◽  
pp. 153303381882431 ◽  
Author(s):  
Yan Chen ◽  
Huiyun Zhu ◽  
Yuqiong Wang ◽  
Yingxiao Song ◽  
Pingping Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Prognostic Factor ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Mitogen Activated Protein Kinase ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cell ◽  
Nuclear Transcription Factor ◽  
Mitogen Activated Protein

The role of microRNA-132 in human pancreatic ductal adenocarcinomas is still ambiguous. We explored the association between microRNA-132 and pancreatic ductal adenocarcinoma prognosis. The expression of microRNA-132 in 50 pancreatic ductal adenocarcinoma tissue samples and pancreatic ductal adenocarcinoma cell lines was examined, and the association between its expression and pancreatic ductal adenocarcinoma prognosis was assessed. Functional analysis and factors downstream of microRNA-132 were investigated. Kaplan-Meier survival curves showed that high expression of microRNA-132 was a significant prognostic factor for 1-year survival of patients with pancreatic ductal adenocarcinoma ( P = .028). Multivariate analysis for overall survival indicated that high expression of microRNA-132 was an independent prognostic factor for patients with pancreatic ductal adenocarcinoma ( P = .044). Low expression of microRNA-132 was associated with poor prognosis in pancreatic ductal adenocarcinoma. Ectopic expression of microRNA-132 significantly inhibited proliferation and promoted apoptosis of 2 pancreatic ductal adenocarcinoma cell lines. Bioinformatic analysis revealed that microRNA-132 may exert its effects on pancreatic ductal adenocarcinoma through downregulating mitogen-activated protein kinase 3 and nuclear transcription factor Y subunit α. The results of this study further our understanding of the relationship between microRNA-132 and pancreatic ductal adenocarcinoma by showing that microRNA-132 might inhibit the progression of pancreatic ductal adenocarcinoma by regulating mitogen-activated protein kinase and nuclear transcription factor Y subunit alpha.

scholarly journals An ultrasensitive fiveplex activity assay for cellular kinases

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christian M. Smolko ◽  
Kevin A. Janes
Keyword(s):  
Protein Kinase ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Large Scale ◽  
Cell Types ◽  
Mitogen Activated Protein Kinase ◽  
Activity Measurement ◽  
Kinase Substrate ◽  
Iκb Kinase ◽  
Mitogen Activated Protein

AbstractProtein kinases are enzymes whose abundance, protein-protein interactions, and posttranslational modifications together determine net signaling activity in cells. Large-scale data on cellular kinase activity are limited, because existing assays are cumbersome, poorly sensitive, low throughput, and restricted to measuring one kinase at a time. Here, we surmount the conventional hurdles of activity measurement with a multiplexing approach that leverages the selectivity of individual kinase-substrate pairs. We demonstrate proof of concept by designing an assay that jointly measures activity of five pleiotropic signaling kinases: Akt, IκB kinase (IKK), c-jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK)-extracellular regulated kinase kinase (MEK), and MAPK-activated protein kinase-2 (MK2). The assay operates in a 96-well format and specifically measures endogenous kinase activation with coefficients of variation less than 20%. Multiplex tracking of kinase-substrate pairs reduces input requirements by 25-fold, with ~75 µg of cellular extract sufficient for fiveplex activity profiling. We applied the assay to monitor kinase signaling during coxsackievirus B3 infection of two different host-cell types and identified multiple differences in pathway dynamics and coordination that warrant future study. Because the Akt–IKK–JNK–MEK–MK2 pathways regulate many important cellular functions, the fiveplex assay should find applications in inflammation, environmental-stress, and cancer research.

scholarly journals Nerve Growth Factor Activates Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase Pathways To Stimulate CREB Serine 133 Phosphorylation

1998 ◽  
Vol 18 (4) ◽  
pp. 1946-1955 ◽  
Author(s):  
Jun Xing ◽  
Jon M. Kornhauser ◽  
Zhengui Xia ◽  
Elizabeth A. Thiele ◽  
Michael E. Greenberg
Keyword(s):  
Transcription Factor ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Nerve Growth ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Ribosomal S6 Kinase

ABSTRACT The mechanisms by which growth factor-induced signals are propagated to the nucleus, leading to the activation of the transcription factor CREB, have been characterized. Nerve growth factor (NGF) was found to activate multiple signaling pathways that mediate the phosphorylation of CREB at the critical regulatory site, serine 133 (Ser-133). NGF activates the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPKs), which in turn activate the pp90 ribosomal S6 kinase (RSK) family of Ser/Thr kinases, all three members of which were found to catalyze CREB Ser-133 phosphorylation in vitro and in vivo. In addition to the ERK/RSK pathway, we found that NGF activated the p38 MAPK and its downstream effector, MAPK-activated protein kinase 2 (MAPKAP kinase 2), resulting in phosphorylation of CREB at Ser-133. Inhibition of either the ERK/RSK or the p38/MAPKAP kinase 2 pathway only partially blocked NGF-induced CREB Ser-133 phosphorylation, suggesting that either pathway alone is sufficient for coupling the NGF signal to CREB activation. However, inhibition of both the ERK/RSK and the p38/MAPKAP kinase 2 pathways completely abolished NGF-induced CREB Ser-133 phosphorylation. These findings indicate that NGF activates two distinct MAPK pathways, both of which contribute to the phosphorylation of the transcription factor CREB and the activation of immediate-early genes.

Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A

2001 ◽  
Vol 359 (3) ◽  
pp. 497-505 ◽  
Author(s):  
Sunke HIMPEL ◽  
Pascal PANZER ◽  
Klaus EIRMBTER ◽  
Hanna CZAJKOWSKA ◽  
Muhammed SAYED ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Mammalian Cells ◽  
Catalytic Domain ◽  
Molecular Model ◽  
Enzymic Activity ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Family ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Protein kinases of the DYRK (‘dual-specificity tyrosine-regulated kinase’) family are characterized by a conserved Tyr-Xaa-Tyr motif (Tyr-319–Tyr-321) in a position exactly corresponding to the activation motif of the mitogen-activated protein kinase (MAP kinase) family (Thr-Xaa-Tyr). In a molecular model of the catalytic domain of DYRK1A, the orientation of phosphorylated Tyr-321 is strikingly similar to that of Tyr-185 in the known structure of the activated MAP kinase, extracellular-signal-regulated kinase 2. Consistent with our model, substitution of Tyr-321 but not of Tyr-319 by phenylalanine markedly reduced the enzymic activity of recombinant DYRK1A expressed in either Escherichia coli or mammalian cells. Direct identification of phosphorylated residues by tandem MS confirmed that Tyr-321, but not Tyr-319, was phosphorylated. When expressed in COS-7 cells, DYRK1A was found to be fully phosphorylated on Tyr-321. A catalytically inactive mutant of DYRK1A contained no detectable phosphotyrosine, indicating that Tyr-321 is autophosphorylated by DYRK1A. MS identified Tyr-111 and Ser-97 as additional autophosphorylation sites in the non-catalytic N-terminal domain of bacterially expressed DYRK1A. Enzymic activity was not affected in the DYRK1A-Y111F mutant. The present experimental data and the molecular model indicate that the activity of DYRK1A is dependent on the autophosphorylation of a conserved tyrosine residue in the activation loop.

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