α1-Adrenergic activation of myocardial Na-K-2Cl cotransport involving mitogen-activated protein kinase

1998 ◽  
Vol 275 (2) ◽  
pp. H641-H652 ◽  
Author(s):  
Geir Øystein Andersen ◽  
Mette Enger ◽  
G. Hege Thoresen ◽  
Tor Skomedal ◽  
Jan-Bjørn Osnes
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal ◽  
Rat Hearts ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Β Blocker ◽  
Map Kinase Pathway ◽  
Erk Activity

The translocation mechanisms involved in the α1-adrenoceptor-stimulated efflux of the potassium analog86Rb+were studied in isolated rat hearts. Phenylephrine (in the presence of a β-blocker) increased the efflux of86Rb+and42K+, and the Na-K-2Cl (or K-Cl) cotransport inhibitor bumetanide reduced the response by 42 ± 11%. Furosemide inhibited the response with a lower potency than that of bumetanide. The bumetanide-insensitive efflux was largely sensitive to the K+ channel inhibitor 4-aminopyridine. Inhibitors of the Na+/H+exchanger or the Na+-K+pump had no effect on the increased86Rb+efflux. The activation of the Na-K-2Cl cotransporter was dependent on the extracellular signal-regulated kinase (ERK) subgroup of the mitogen-activated protein (MAP) kinase family. Phenylephrine stimulation increased ERK activity 3.4-fold. PD-98059, an inhibitor of the ERK cascade, reduced both the increased86Rb+efflux and ERK activity. Specific inhibitors of protein kinase C and Ca2+/calmodulin-dependent kinase II had no effect. In conclusion, α1-adrenoceptor stimulation increases86Rb+efflux from the rat heart via K+channels and a Na-K-2Cl cotransporter. Activation of the Na-K-2Cl cotransporter is apparently dependent on the MAP kinase pathway.

scholarly journals A Mitogen-Activated Protein Kinase That Senses Nitrogen Regulates Conidial Germination and Growth in Aspergillus fumigatus

2004 ◽  
Vol 3 (2) ◽  
pp. 557-560 ◽  
Author(s):  
Tao Xue ◽  
C. Kim Nguyen ◽  
Angela Romans ◽  
Gregory S. May
Keyword(s):  
Protein Kinase ◽  
Aspergillus Fumigatus ◽  
Map Kinase ◽  
Conidial Germination ◽  
Mitogen Activated Protein Kinase ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Map Kinase Pathway ◽  
Germination And Growth ◽  
Kinase Pathway

ABSTRACT We show that the mitogen-activated protein (MAP) kinase pathway that responds to osmotic stress in Aspergillus fumigatus is also involved in nutritional sensing. This MAP kinase regulates conidial germination in response to the nitrogen source and is activated upon starvation for either carbon or nitrogen during vegetative growth.

scholarly journals RACK1 Targets the Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway To Link Integrin Engagement with Focal Adhesion Disassembly and Cell Motility

2007 ◽  
Vol 27 (23) ◽  
pp. 8296-8305 ◽  
Author(s):  
Tomas Vomastek ◽  
Marcin P. Iwanicki ◽  
Hans-Joerg Schaeffer ◽  
Adel Tarcsafalvi ◽  
J. Thomas Parsons ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Mitogen Activated Protein Kinase ◽  
Erk Pathway ◽  
Large Measure ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Erk Activity

ABSTRACT The extracellular signal-regulated kinase (ERK) cascade is activated in response to a multitude of extracellular signals and converts these signals into a variety of specific biological responses, including cell differentiation, cell movement, cell division, and apoptosis. The specificity of the biological response is likely to be controlled in large measure by the localization of signaling, thus enabling ERK activity to be directed towards specific targets. Here we show that the RACK1 scaffold protein functions specifically in integrin-mediated activation of the mitogen-activated protein kinase/ERK cascade and targets active ERK to focal adhesions. We found that RACK1 associated with the core kinases of the ERK pathway, Raf, MEK, and ERK, and that attenuation of RACK1 expression resulted in a decrease in ERK activity in response to adhesion but not in response to growth factors. RACK1 silencing also caused a reduction of active ERK in focal adhesions, an increase in focal adhesion length, a decreased rate of focal adhesion disassembly, and decreased motility. Our data further suggest that focal adhesion kinase is an upstream activator of the RACK1/ERK pathway. We suggest that RACK1 tethers the ERK pathway core kinases and channels signals from upstream activation by integrins to downstream targets at focal adhesions.

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.

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.

scholarly journals Role of MLK3 in the Regulation of Mitogen-Activated Protein Kinase Signaling Cascades

2005 ◽  
Vol 25 (9) ◽  
pp. 3670-3681 ◽  
Author(s):  
Deborah Brancho ◽  
Juan-Jose Ventura ◽  
Anja Jaeschke ◽  
Beth Doran ◽  
Richard A. Flavell ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Selective Reduction ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascades ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Jnk Activation ◽  
Protein Kinase Signaling

ABSTRACT Mixed-lineage protein kinase 3 (MLK3) is a member of the mitogen-activated protein (MAP) kinase kinase kinase group that has been implicated in multiple signaling cascades, including the NF-κB pathway and the extracellular signal-regulated kinase, c-Jun NH2-terminal kinase (JNK), and p38 MAP kinase pathways. Here, we examined the effect of targeted disruption of the murine Mlk3 gene. Mlk3 −/− mice were found to be viable and healthy. Primary embryonic fibroblasts prepared from these mice exhibited no major signaling defects. However, we did find that MLK3 deficiency caused a selective reduction in tumor necrosis factor (TNF)-stimulated JNK activation. Together, these data demonstrate that MLK3 contributes to the TNF signaling pathway that activates JNK.

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 ras2 Controls Morphogenesis, Pheromone Response, and Pathogenicity in the Fungal Pathogen Ustilago maydis

2002 ◽  
Vol 1 (6) ◽  
pp. 954-966 ◽  
Author(s):  
Nancy Lee ◽  
James W. Kronstad
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Ustilago Maydis ◽  
Mitogen Activated Protein Kinase ◽  
Gene Encoding ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Map Kinase Pathway ◽  
Altered Cell ◽  
Kinase Pathway

ABSTRACT Ustilago maydis, a pathogen of maize, is a useful model for the analysis of mating, pathogenicity, and the morphological transition between budding and filamentous growth in fungi. As in other fungi, these processes are regulated by conserved signaling mechanisms, including the cyclic AMP (cAMP)/protein kinase A (PKA) pathway and at least one mitogen-activated protein kinase (MAP kinase) pathway. A current challenge is to identify additional factors that lie downstream of the cAMP pathway and that influence morphogenesis in U. maydis. In this study, we identified suppressor mutations that restored budding growth to a constitutively filamentous mutant with a defect in the gene encoding a catalytic subunit of PKA. Complementation of one suppressor mutation unexpectedly identified the ras2 gene, which is predicted to encode a member of the well-conserved ras family of small GTP-binding proteins. Deletion of the ras2 gene in haploid cells altered cell morphology, eliminated pathogenicity on maize seedlings, and revealed a role in the production of aerial hyphae during mating. We also used an activated ras2 allele to demonstrate that Ras2 promotes pseudohyphal growth via a MAP kinase cascade involving the MAP kinase kinase Fuz7 and the MAP kinase Ubc3. Overall, our results reveal an additional level of crosstalk between the cAMP signaling pathway and a MAP kinase pathway influenced by Ras2.

Phosphatidylinositol 3-kinases regulate ERK and p38 MAP kinases in canine colonic smooth muscle

2000 ◽  
Vol 279 (2) ◽  
pp. C352-C360 ◽  
Author(s):  
Ilia A. Yamboliev ◽  
Kevin M. Wiesmann ◽  
Cherie A. Singer ◽  
Jason C. Hedges ◽  
William T. Gerthoffer
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Map Kinases ◽  
Calf Serum ◽  
Specific Effect ◽  
Kinase C ◽  
Extracellular Signal ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Intact Muscle

In canine colon, M2/M3 muscarinic receptors are coupled to extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinases. We tested the hypothesis that this coupling is mediated by enzymes of the phosphatidylinositol (PI) 3-kinase family. RT-PCR and Western blotting demonstrated expression of two isoforms, PI 3-kinase-α and PI 3-kinase-γ. Muscarinic stimulation of intact muscle strips (10 μM ACh) activated PI 3-kinase-γ, ERK and p38 MAP kinases, and MAP kinase-activated protein kinase-2, whereas PI 3-kinase-α activation was not detected. Wortmannin (25 μM) abolished the activation of PI 3-kinase-γ, ERK, and p38 MAP kinases. MAP kinase inhibition was a PI 3-kinase-γ-specific effect, since wortmannin did not inhibit recombinant activated murine ERK2 MAP kinase, protein kinase C, Raf-1, or MAP kinase kinase. In cultured muscle cells, newborn calf serum (3%) activated PI 3-kinase-α and PI 3-kinase-γ isoforms, ERK and p38 MAP kinases, and stimulated chemotactic cell migration. Using wortmannin and LY-294002 to inhibit PI 3-kinase activity and PD-098059 and SB-203580 to inhibit ERK and p38 MAP kinases, we established that these enzymes are functionally important for regulation of chemotactic migration of colonic myocytes.

scholarly journals Dual phosphorylation and autophosphorylation in mitogen-activated protein (MAP) kinase activation

1993 ◽  
Vol 296 (1) ◽  
pp. 25-31 ◽  
Author(s):  
J H Her ◽  
S Lakhani ◽  
K Zu ◽  
J Vila ◽  
P Dent ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Specific Protein ◽  
Enzymic Activity ◽  
Extracellular Signal ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Catalytic Loop

p42mapk [mitogen activated protein (MAP) kinase; extracellular signal-regulated protein kinase (ERK)] is a serine/threonine-specific protein kinase that is activated by dual tyrosine and threonine phosphorylation in response to diverse agonists. Both the tyrosine and threonine phosphorylations are necessary for full enzymic activity. A MAP kinase activator recently purified and cloned has been shown to be a protein kinase (MAP kinase kinase) that is able to induce the dual phosphorylation of MAP kinase on both the regulatory tyrosine and threonine sites in vitro. In the present paper we have utilized MAP kinase mutants altered in the sites of regulatory phosphorylation to show, both in vivo and in vitro, that phosphorylation of the tyrosine and the threonine can occur independently of one another, with no required order of phosphorylation. We also utilized kinase-defective variants of MAP kinase with mutations in either the ATP-binding loop or the catalytic loop, and obtained data suggesting that the activity or structure of the catalytic loop of MAP kinase plays an important role in its own dual phosphorylation.

scholarly journals Inhibition of c-Jun DNA binding by mitogen-activated protein kinase.

1992 ◽  
Vol 3 (10) ◽  
pp. 1117-1130 ◽  
Author(s):  
S Y Chou ◽  
V Baichwal ◽  
J E Ferrell
Keyword(s):  
Protein Kinase ◽  
Dna Binding ◽  
Map Kinase ◽  
Single Site ◽  
Mitogen Activated Protein Kinase ◽  
Response Element ◽  
Transcriptional Initiation ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Lines Of Evidence

Here we demonstrate that partially purified Xenopus p42 mitogen-activated protein (MAP) kinase phosphorylates bacterially expressed human c-Jun at a single site, serine 243. Several lines of evidence argue that this phosphorylation is due to p42 MAP kinase itself rather than some contaminating species. Phosphorylation of serine 243 markedly decreases the binding of c-Jun to oligonucleotides containing the 12-O-tetradecanoylphorbol-13-acetate response element. These findings suggest that MAP kinase may play a role in the down-regulation of c-Jun or in the cycle of transcriptional initiation and elongation.

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