scholarly journals Gα5 subunit-mediated signalling requires a D-motif and the MAPK ERK1 in Dictyostelium

Microbiology ◽  
2010 ◽  
Vol 156 (3) ◽  
pp. 789-797 ◽  
Author(s):  
Brent Raisley ◽  
Hoai-Nghia Nguyen ◽  
Jeffrey A. Hadwiger
Keyword(s):  
Gene Expression ◽  
Mitogen Activated Protein Kinase ◽  
Aggregate Formation ◽  
Developmental Gene ◽  
Multicellular Development ◽  
Extracellular Signal Regulated Kinase ◽  
Developmental Gene Expression ◽  
Amino Terminal ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

The Dictyostelium Gα5 subunit has been shown to reduce cell viability, inhibit folate chemotaxis and accelerate tip morphogenesis and gene expression during multicellular development. Alteration of the D-motif (mitogen-activated protein kinase docking site) at the amino terminus of the Gα5 subunit or the loss of extracellular signal-regulated kinase (ERK)1 diminished the lethality associated with the overexpression or constitutive activation of the Gα5 subunit. The amino-terminal D-motif of the Gα5 subunit was also found to be necessary for the reduced cell size, small aggregate formation and precocious developmental gene expression associated with Gα5 subunit overexpression. This D-motif also contributed to the aggregation delay in cells expressing a constitutively active Gα5 subunit, but the D-motif was not necessary for the inhibition of folate chemotaxis. These results suggest that the amino-terminal D-motif is required for some but not all phenotypes associated with elevated Gα5 subunit functions during growth and development and that ERK1 can function in Gα5 subunit-mediated signal transduction.

Phorbol ester-induced activation of mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase and extracellular-signal-regulated protein kinase decreases glucose-6-phosphatase gene expression

2001 ◽  
Vol 357 (3) ◽  
pp. 867-873 ◽  
Author(s):  
Dieter SCHMOLL ◽  
Rolf GREMPLER ◽  
Andreas BARTHEL ◽  
Hans-Georg JOOST ◽  
Reinhard WALTHER
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Regulation Of Gene Expression ◽  
Insulin Response ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Glucose-6-phosphatase (G6Pase) plays a central role in blood glucose homoeostasis, and insulin suppresses G6Pase gene expression by the activation of phosphoinositide 3-kinase (PI 3-kinase). Here, we show that the phorbol ester PMA decreases both basal and dexamethasone/cAMP-induced expression of a luciferase gene under the control of the G6Pase promoter in transiently transfected H4IIE hepatoma cells. This regulation was suppressed by the inhibitors of the mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase (MEK), PD98059 and U0126, but not by the inhibitor of PI 3-kinase, LY294002. The co-expression of a constitutively active mutant of MEK mimicked the regulation of G6Pase promoter activity by PMA. The effect of PMA on both basal and induced G6Pase gene transcription was impaired by the overexpression of a dominant negative MEK construct, as well as by the expression of mitogen-activated protein kinase phosphatase-1. The mutation of the forkhead-binding sites within the insulin-response unit of the G6Pase promoter, which decreases the effect of insulin on G6Pase gene expression, did not alter the regulation of gene expression by PMA. The data show that PMA decreases G6Pase gene expression by the activation of MEK and extracellular-signal regulated protein kinase. With that, PMA mimics the effect of insulin on G6Pase gene expression by a different signalling pathway.

scholarly journals Isolation and characterization of a Drosophila homologue of mitogen-activated protein kinase phosphatase-3 which has a high substrate specificity towards extracellular-signal-regulated kinase

2001 ◽  
Vol 361 (1) ◽  
pp. 143-151 ◽  
Author(s):  
Sun-Hong KIM ◽  
Hyung-Bae KWON ◽  
Yong-Sik KIM ◽  
Ji-Hwan RYU ◽  
Kyung-Sub KIM ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Expressed Sequence Tag ◽  
Mitogen Activated Protein Kinase ◽  
Calculated Molecular Mass ◽  
Extracellular Signal Regulated Kinase ◽  
Isolation And Characterization ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

A partial C-terminal cDNA sequence of a novel Drosophila mitogen-activated protein kinase phosphatase (MKP), designated DMKP-3, was identified from an epitope expressed sequence tag database, and the missing N-terminal cDNA fragment was cloned from a Drosophila cDNA library. DMKP-3 is a protein of 411 amino acids, with a calculated molecular mass of 45.8kDa; the deduced amino acid sequence is most similar to that of mammalian MKP-3. Recombinant DMKP-3 produced in Escherichia coli retained intrinsic tyrosine phosphatase activity. In addition, DMKP-3 specifically inhibited extracellular-signal-regulated kinase (ERK) activity, but was without a significant affect on c-Jun N-terminal kinase (JNK) and p38 activities, when it was overexpressed in Schneider cells. DMKP-3 interacted specifically with Drosophila ERK (DERK) via its N-terminal domain. In addition, DMKP-3 specifically inhibited Elk-1-dependent trans-reporter gene expression in mammalian CV1 cells, and dephosphorylated activated mammalian ERK in vitro. DMKP-3 is uniquely localized in the cytoplasm within Schneider cells, and gene expression is tightly regulated during development. Thus DMKP-3 is a Drosophila homologue of mammalian MKP-3, and may play important roles in the regulation of various developmental processes.

scholarly journals Extracellular Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Gene Expression

2019 ◽  
Vol 20 (15) ◽  
pp. 3792 ◽  
Author(s):  
Nathan Lu ◽  
Charles J. Malemud
Keyword(s):  
Gene Expression ◽  
Critical Role ◽  
Cell Receptor ◽  
Bone Cell ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascade ◽  
Extracellular Signal Regulated Kinase ◽  
Cellular Events ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase family of signaling molecules. ERK is predominantly found in two forms, ERK1 (p44) and ERK2 (p42), respectively. There are also several atypical forms of ERK, including ERK3, ERK4, ERK5 and ERK7. The ERK1/2 signaling pathway has been implicated in many and diverse cellular events, including proliferation, growth, differentiation, cell migration, cell survival, metabolism and transcription. ERK1/2 is activated (i.e., phosphorylated) in the cytosol and subsequently translocated to the nucleus, where it activates transcription factors including, but not limited to, ETS, c-Jun, and Fos. It is not surprising that the ERK1/2 signaling cascade has been implicated in many pathological conditions, namely, cancer, arthritis, chronic inflammation, and osteoporosis. This narrative review examines many of the cellular events in which the ERK1/2 signaling cascade plays a critical role. It is anticipated that agents designed to inhibit ERK1/2 activation or p-ERK1/2 activity will be developed for the treatment of those diseases characterized by dysregulated gene expression through ERK1/2 activation.

scholarly journals Activation of μ-Opioid Receptor Induces Expression of c-fos  and junB  via  Mitogen-activated Protein Kinase Cascade

2001 ◽  
Vol 95 (4) ◽  
pp. 983-989 ◽  
Author(s):  
Takehiro Shoda ◽  
Kazuhiko Fukuda ◽  
Hisatoshi Uga ◽  
Hiroyuki Mima ◽  
Hitoshi Morikawa
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Mu Opioid ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Kinase Cascade

Background Opioid-induced long-term functional alterations of the nervous system, such as tolerance, addiction, and dependence, conceivably involve changes in gene expression. The authors have previously reported that opioid receptors are functionally coupled to extracellular signal-regulated kinase, a class of the mitogen-activated protein kinase. To address whether activation of the opioid receptor induces changes in gene expression through the activation of extracellular signal-regulated kinase, the authors examined mu-opioid receptor (MOR)-induced immediate early gene expression. Methods Chinese hamster ovary cells stably expressing MOR were used. Cells were stimulated by MOR agonists after 24-h serum starvation. Expression of c-fos and junB genes was analyzed by RNA blot hybridization. To explore the mechanism of MOR-mediated c-fos and junB expression, activity of a transcription factor, Elk-1, was assessed by reporter assay. Furthermore, to investigate the functional consequences of c-fos and junB induction, MOR-mediated formation of the functional transcription factor complex AP-1 was examined by reporter assay and electrophoretic mobility shift assay. Results Mu-opioid receptor activation induced c-fos and junB messenger RNAs, which were inhibited by pretreatment of the cells with pertussis toxin and PD98059, an inhibitor of extracellular signal-regulated kinase cascade. MOR stimulation elevated Elk-1-mediated transcriptional activity by about 10-fold. AP-1-mediated transcriptional activity was stimulated by MOR agonists by about twofold. Electrophoretic mobility shift assay revealed that AP-1 binding activity in the nuclear extract was elevated by MOR activation and further showed that products of c-fos and junB genes are involved in formation of AP-1 complex. Conclusions Mu-opioid receptor activation induces c-fos and junB expression and elevates AP-1-mediated transcriptional activities via the mitogen-activated protein kinase cascade.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

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