scholarly journals The Cloned Thrombin Receptor Is Necessary and Sufficient for Activation of Mitogen-activated Protein Kinase and Mitogenesis in Mouse Lung Fibroblasts

1996 ◽  
Vol 271 (35) ◽  
pp. 21536-21541 ◽  
Author(s):  
JoAnn Trejo ◽  
Andrew J. Connolly ◽  
Shaun R. Coughlin
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Lung Fibroblasts ◽  
Mouse Lung ◽  
Thrombin Receptor ◽  
Mitogen Activated Protein ◽  
Necessary And Sufficient

scholarly journals Phosphorylation of Ago2 and Subsequent Inactivation of let-7a RNP-Specific MicroRNAs Control Differentiation of Mammalian Sympathetic Neurons

2016 ◽  
Vol 36 (8) ◽  
pp. 1260-1271 ◽  
Author(s):  
Somi Patranabis ◽  
Suvendra Nath Bhattacharyya
Keyword(s):  
Protein Kinase ◽  
Neuronal Differentiation ◽  
Sympathetic Neurons ◽  
Neuronal Cells ◽  
Cellular Level ◽  
Mitogen Activated Protein Kinase ◽  
Animal Cells ◽  
Mitogen Activated Protein ◽  
Small Regulatory Rnas ◽  
Necessary And Sufficient

MicroRNAs (miRNAs) are small regulatory RNAs that regulate gene expression posttranscriptionally by base pairing to the target mRNAs in animal cells.KRas, an oncogene known to be repressed by let-7a miRNAs, is expressed and needed for the differentiation of mammalian sympathetic neurons and PC12 cells. We documented a loss of let-7a activity during this differentiation process without any significant change in the cellular level of let-7a miRNA. However, the level of Ago2, an essential component that is associated with miRNAs to form RNP-specific miRNA (miRNP) complexes, shows an increase with neuronal differentiation. In this study, differentiation-induced phosphorylation and the subsequent loss of miRNA from Ago2 were noted, and these accounted for the loss of miRNA activity in differentiating neurons. Neuronal differentiation induces the phosphorylation of mitogen-activated protein kinase p38 and the downstream kinase mitogen- and stress-activated protein kinase 1 (MSK1). This in turn upregulates the phosphorylation of Ago2 and ensures the dissociation of miRNA from Ago2 in neuronal cells. MSK1-mediated miRNP inactivation is a prerequisite for the differentiation of neuronal cells, where let-7a miRNA gets unloaded from Ago2 to ensure the upregulation ofKRas, a target of let-7a. We noted that the inactivation of let-7a is both necessary and sufficient for the differentiation of sympathetic neurons.

scholarly journals Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells

2002 ◽  
Vol 366 (3) ◽  
pp. 737-744 ◽  
Author(s):  
Takanori KITAMURA ◽  
Kazuhiro KIMURA ◽  
Bae Dong JUNG ◽  
Kennedy MAKONDO ◽  
Naoki SAKANE ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mouse Lung ◽  
Camp Response Element ◽  
Site Specific ◽  
C Peptide ◽  
Mitogen Activated Protein ◽  
Capillary Endothelial Cells ◽  
Kinase Pathway ◽  
Stimulation Of

Proinsulin C-peptide has been reported to have some biological activities and to be possibly involved in the development of diabetic microangiopathy. In the present study, we examined the effects of C-peptide on the mitogen-activated protein kinase pathway in LEII mouse lung capillary endothelial cells. Stimulation of the cells with C-peptide increased both p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK1/2) activities and activity-related site-specific phosphorylation of the respective kinases in a concentration-dependent manner, but failed to activate c-Jun N-terminal kinase. Stimulation of the cells with C-peptide also induced site-specific phosphorylation of cAMP response element (CRE)-binding protein (CREB)/activating transcription factor 1 (ATF1), and thereby binding of these transcription factors to CRE. Among three CREB kinases tested, phosphorylation of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) was induced after stimulation with C-peptide. The phosphorylation of CREB, ATF1 and MAPKAP-K2 were inhibited by SB203580, a p38MAPK inhibitor, but not by PD98059, an ERK kinase inhibitor. These results indicate that C-peptide activates p38MAPK followed by MAPKAP-K2 to enhance DNA—CREB/ATF1 interactions.

scholarly journals Store-operated Ca2+ Entry (SOCE) Induced by Protease-activated Receptor-1 Mediates STIM1 Protein Phosphorylation to Inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38β Mitogen-activated Protein Kinase

2013 ◽  
Vol 288 (23) ◽  
pp. 17030-17041 ◽  
Author(s):  
Premanand C. Sundivakkam ◽  
Viswanathan Natarajan ◽  
Asrar B. Malik ◽  
Chinnaswamy Tiruppathi
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Transient Receptor Potential ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mouse Lung ◽  
Mitogen Activated Protein ◽  
Protease Activated Receptor 1 ◽  
Amp Activated Protein Kinase

The Ca2+ sensor STIM1 is crucial for activation of store-operated Ca2+ entry (SOCE) through transient receptor potential canonical and Orai channels. STIM1 phosphorylation serves as an “off switch” for SOCE. However, the signaling pathway for STIM1 phosphorylation is unknown. Here, we show that SOCE activates AMP-activated protein kinase (AMPK); its effector p38β mitogen-activated protein kinase (p38β MAPK) phosphorylates STIM1, thus inhibiting SOCE in human lung microvascular endothelial cells. Activation of AMPK using 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) resulted in STIM1 phosphorylation on serine residues and prevented protease-activated receptor-1 (PAR-1)-induced Ca2+ entry. Furthermore, AICAR pretreatment blocked PAR-1-induced increase in the permeability of mouse lung microvessels. Activation of SOCE with thrombin caused phosphorylation of isoform α1 but not α2 of the AMPK catalytic subunit. Moreover, knockdown of AMPKα1 augmented SOCE induced by thrombin. Interestingly, SB203580, a selective inhibitor of p38 MAPK, blocked STIM1 phosphorylation and led to sustained STIM1-puncta formation and Ca2+ entry. Of the three p38 MAPK isoforms expressed in endothelial cells, p38β knockdown prevented PAR-1-mediated STIM1 phosphorylation and potentiated SOCE. In addition, inhibition of the SOCE downstream target CaM kinase kinase β (CaMKKβ) or knockdown of AMPKα1 suppressed PAR-1-mediated phosphorylation of p38β and hence STIM1. Thus, our findings demonstrate that SOCE activates CaMKKβ-AMPKα1-p38β MAPK signaling to phosphorylate STIM1, thereby suppressing endothelial SOCE and permeability responses.

scholarly journals The p42/p44 MAP Kinase Pathway Prevents Apoptosis Induced by Anchorage and Serum Removal

2000 ◽  
Vol 11 (3) ◽  
pp. 1103-1112 ◽  
Author(s):  
Maude Le Gall ◽  
Jean-Claude Chambard ◽  
Jean-Philippe Breittmayer ◽  
Dominique Grall ◽  
Jacques Pouysségur ◽  
...  
Keyword(s):  
Cell Death ◽  
Growth Factor ◽  
Protein Kinase ◽  
Annexin V ◽  
Mitogen Activated Protein Kinase ◽  
Lung Fibroblasts ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Chimeric Construct ◽  
Caspase Substrate

Anchorage removal like growth factor removal induces apoptosis. In the present study we have characterized signaling pathways that can prevent this cell death using a highly growth factor– and anchorage-dependent line of lung fibroblasts (CCL39). After anchorage removal from exponentially growing cells, annexin V-FITC labeling can be detected after 8 h. Apoptosis was confirmed by analysis of sub-G1 DNA content and Western blotting of the caspase substrate poly (ADP-ribose) polymerase. Growth factor withdrawal accelerates and potentiates suspension-induced cell death. Activation of Raf-1 kinase in suspension cultures of CCL39 or Madin–Darby canine kidney cells stably expressing an estrogen-inducible activated–Raf-1 construct (ΔRaf-1:ER) suppresses apoptosis induced by growth factor and/or anchorage removal. This protective effect appears to be mediated by the Raf, mitogen- or extracellular signal–regulated kinase kinase (MEK), and mitogen-activated protein kinase module because it is sensitive to pharmacological inhibition of MEK-1 and it can be mimicked by expression of constitutively active MEK-1 in CCL39 cells. Finally, apoptosis induced by disruption of the actin cytoskeleton with the Rho-directed toxin B (Clostridium difficile) is prevented by activation of the ΔRaf-1:ER chimeric construct. These findings highlight the ability of p42/p44 mitogen-activated protein kinase to generate survival signals that counteract cell death induced by loss of matrix contact, cytoskeletal integrity, and extracellular mitogenic factors.

scholarly journals Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells.

1996 ◽  
Vol 7 (11) ◽  
pp. 1679-1690 ◽  
Author(s):  
G R Post ◽  
L R Collins ◽  
E D Kennedy ◽  
S A Moskowitz ◽  
A M Aragay ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Dna Synthesis ◽  
Pertussis Toxin ◽  
Mitogen Activated Protein Kinase ◽  
Thrombin Receptor ◽  
Protein Kinase Activity ◽  
Astrocytoma Cells ◽  
Mitogen Activated Protein ◽  
1321N1 Astrocytoma

In 1321N1 astrocytoma cells, thrombin, but not carbachol, induces AP-1-mediated gene expression and DNA synthesis. To understand the divergent effects of these G protein-coupled receptor agonists on cellular responses, we examined Gq-dependent signaling events induced by thrombin receptor and muscarinic acetylcholine receptor stimulation. Thrombin and carbachol induce comparable changes in phosphoinositide and phosphatidylcholine hydrolysis, mobilization of intracellular Ca2+, diglyceride generation, and redistribution of protein kinase C; thus, activation of these Gq-signaling pathways appears to be insufficient for gene expression and mitogenesis. Thrombin increases Ras and mitogen-activated protein kinase activation to a greater extent than carbachol in 1321N1 cells. The effects of thrombin are not mediated through Gi, since ribosylation of Gi/Go proteins by pertussis toxin does not prevent thrombin-induced gene expression or thrombin-stimulated DNA synthesis. We recently reported that the pertussis toxin-insensitive G12 protein is required for thrombin-induced DNA synthesis. We demonstrate here, using transfection of receptors and G proteins in COS-7 cells, that G alpha 12 selectively couples the thrombin receptor to AP-1-mediated gene expression. This does not appear to result from increased mitogen-activated protein kinase activity but may reflect activation of a tyrosine kinase pathway. We suggest that preferential coupling of the thrombin receptor to G12 accounts for the selective ability of thrombin to stimulate Ras, mitogen-activated protein kinase, gene expression, and mitogenesis in 1321N1 cells.

scholarly journals Protective role of PI3-kinase/Akt/eNOS signaling in mechanical stress through inhibition of p38 mitogen-activated protein kinase in mouse lung

2010 ◽  
Vol 31 (2) ◽  
pp. 175-183 ◽  
Author(s):  
Xin-qi Peng ◽  
Mahendra Damarla ◽  
Jarrett Skirball ◽  
Stephanie Nonas ◽  
Xiao-ying Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mechanical Stress ◽  
Protective Role ◽  
Pi3 Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mouse Lung ◽  
Mitogen Activated Protein
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