scholarly journals Elevation of Intracellular Na+ Contributes to Expression of Early Response Genes Triggered by Endothelial Cell Shrinkage

2019 ◽  
Vol 53 (4) ◽  
pp. 638-647 ◽  
Keyword(s):  
Endothelial Cell ◽  
Early Response ◽  
Cell Shrinkage ◽  
Early Response Genes

scholarly journals Endogenous non-cyclooxygenase metabolites of arachidonic acid modulate growth and mRNA levels of immediate-early response genes in rat mesangial cells

1991 ◽  
Vol 266 (6) ◽  
pp. 3800-3807
Author(s):  
A Sellmayer ◽  
W M Uedelhoven ◽  
P C Weber ◽  
J V Bonventre
Keyword(s):  
Arachidonic Acid ◽  
Mesangial Cells ◽  
Early Response ◽  
Immediate Early ◽  
Mrna Levels ◽  
Early Response Genes

Promiscuous and Depolarization-Induced Immediate-Early Response Genes Are Induced by Mechanical Strain of Osteoblasts

2009 ◽  
Vol 24 (7) ◽  
pp. 1247-1262 ◽  
Author(s):  
Claus-Eric Ott ◽  
Sebastian Bauer ◽  
Thomas Manke ◽  
Susan Ahrens ◽  
Christian Rödelsperger ◽  
...  
Keyword(s):  
Mechanical Strain ◽  
Early Response ◽  
Immediate Early ◽  
Early Response Genes

Expression of early response genes after massive hepatectomy in rats

1995 ◽  
Vol 108 (4) ◽  
pp. A1142
Author(s):  
Y. Panis ◽  
N. Lomri ◽  
J.C. Emond
Keyword(s):  
Early Response ◽  
Massive Hepatectomy ◽  
Early Response Genes

scholarly journals Inhibition of Early Response Genes Prevents Changes in Global Joint Metabolomic Profiles in Mouse Post-Traumatic Osteoarthritis

2018 ◽  
Author(s):  
Dominik R. Haudenschild ◽  
Alyssa K. Carlson ◽  
Donald L. Zignego ◽  
Jasper H.N. Yik ◽  
Jonathan K. Hilmer ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Cellular Responses ◽  
Early Response ◽  
Primary Response ◽  
Response Gene ◽  
Joint Injury ◽  
Non Invasive ◽  
Primary Response Gene ◽  
Post Traumatic ◽  
Early Response Genes

Osteoarthritis (OA) is the most common degenerative joint disease, and joint injury increases the risk of OA by 10-fold. Although the injury event itself damages joint tissues, a substantial amount of secondary damage is mediated by the cellular responses to the injury. Cellular responses include the production and activation of proteases (MMPs, ADAMTSs, Cathepsins), the production of inflammatory cytokines, and we hypothesize, changes to the joint metabolome. The trajectory of cellular responses is driven by the transcriptional activation of early response genes, which requires Cdk9-dependent RNA Polymerase II phosphorylation. Flavopiridol is a potent and selective inhibitor of Cdk9 kinase activity, which prevents the transcriptional activation of early response genes. To model post-traumatic osteoarthritis, we subjected mice to non-invasive ACL-rupture joint injury. Following injury, mice were treated with flavopiridol to inhibit Cdk9-dependent transcriptional activation, or vehicle control. Global joint metabolomics were analyzed 1 hour after injury. We found that injury induced metabolomic changes, including increases in Vitamin D3 metabolism and others. Importantly, we found that inhibition of primary response gene activation at the time of injury largely prevented the global changes in the metabolomics profiles. Cluster analysis of joint metabolomes identified groups of injury-induced and drug-responsive metabolites, which may offer novel targets for cell-mediated secondary joint damage. Metabolomic profiling provides an instantaneous snapshot of biochemical activity representing cellular responses, and these data demonstrate the potential for inhibition of early response genes to alter the trajectory of cell-mediated degenerative changes following joint injury.Significance StatementJoint injury is an excellent predictor of future osteoarthritis. It is increasingly apparent that the acute cellular responses to injury contribute to the initiation and pathogenesis of OA. Although changes to the joint transcriptome have been extensively studied in the context of joint injury, little is known about changes to small-molecule metabolites. Here we use a non-invasive ACL rupture model of joint injury in mice to identify injury-induced changes to the global metabolomic profiles. In one experimental group we prevented the activation of primary response gene transcription using the Cdk9 inhibitor flavopiridol. Through this comparison, we identified two sets of metabolites that change acutely after joint injury: those that require transcription of primary response genes, and those that do not.

scholarly journals Only the Substitution of Methionine 918 with a Threonine and Not with Other Residues Activates RET Transforming Potential*

Endocrinology ◽  
1997 ◽  
Vol 138 (4) ◽  
pp. 1450-1455 ◽  
Author(s):  
Anna Maria Cirafici ◽  
Giuliana Salvatore ◽  
Gabriella De Vita ◽  
Francesca Carlomagno ◽  
Nina A. Dathan ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Point Mutations ◽  
Early Response ◽  
Specific Point ◽  
Medullary Thyroid ◽  
Transforming Activity ◽  
Early Response Genes

Abstract Specific point-mutations of the RET receptor tyrosine kinase protooncogene are responsible for the inheritance of multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B), and familial medullary thyroid carcinoma (FMTC). MEN2B is caused by the substitution of methionine 918 by a threonine in the tyrosine kinase (TK) domain of RET. This mutation converts RET into a dominant transforming oncogene. We have substituted Met918 with four different residues and found that RET acquired transforming activity only when Met918 was substituted with a threonine. However, also when serine and valine, but not leucine or phenylalanine, were inserted in position 918, the RET TK function was activated and induced, especially in the case of the RET(918Ser), immmediate-early response genes. We conclude that the preservation of Met918 is critical for the control of RET kinase. However, only when a threonine residue is present in position 918, does RET efficiently couple with a transforming pathway.

Growth factor-induced delayed early response genes

1992 ◽  
Vol 12 (9) ◽  
pp. 3919-3929
Author(s):  
A Lanahan ◽  
J B Williams ◽  
L K Sanders ◽  
D Nathans
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Early Response ◽  
Integral Membrane Protein ◽  
Early Gene ◽  
Immediate Early ◽  
Human Macrophage ◽  
Cellular Genes ◽  
Gene Response ◽  
Early Response Genes

Growth factors induce the sequential expression of cellular genes whose products are thought to mediate long-term responses to the growth factors. In mouse 3T3 fibroblastic cells, the first genes to be expressed (immediate-early genes) are activated within minutes after the addition of platelet-derived growth factor, fibroblast growth factor, or serum. By cDNA cloning, we have identified genes that are activated after a delay of a few hours and several hours prior to serum-induced DNA replication. Activation of these delayed early response genes requires new protein synthesis, presumably the synthesis of immediate-early transcription factors described previously. Partial or complete sequencing of 13 different delayed early cDNAs, representing about 40% of the 650 primary cDNA isolates, revealed that 8 were related to known gene sequences and 5 were not. Among the former are cDNAs encoding nonhistone chromosomal proteins [HMGI(Y) and HMGI-C], adenine phosphoribosyltransferase (APRT), a protein related to human macrophage migration inhibitory factor (MIF), a protein of the major intrinsic protein (MIP) family homologous to the integral membrane protein of human erythrocytes, and cyclin CYL1. In 3T3 cells, the delayed early gene response to growth factors appears to be at least as complex as the immediate-early gene response previously described.

Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells

1990 ◽  
Vol 10 (10) ◽  
pp. 5324-5332
Author(s):  
J Szeberényi ◽  
H Cai ◽  
G M Cooper
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Morphological Differentiation ◽  
Early Response ◽  
Secondary Response ◽  
Response Gene ◽  
Early Response Gene ◽  
Early Response Genes

A dominant inhibitory mutation of Ha-ras which changes Ser-17 to Asn-17 in the gene product p21 [p21 (Asn-17)Ha-ras] has been used to investigate the role of ras in neuronal differentiation of PC12 cells. The growth of PC12 cells, in contrast to NIH 3T3 cells, was not inhibited by p21(Asn-17)Ha-ras expression. However, PC12 cells expressing the mutant Ha-ras protein showed a marked inhibition of morphological differentiation induced by nerve growth factor (NGF) or fibroblast growth factor (FGF). These cells, however, were still able to respond with neurite outgrowth to dibutyryl cyclic AMP and 12-O-tetradecanoylphorbol-13-acetate (TPA). Induction of early-response genes (fos, jun, and zif268) by NGF and FGF but not by TPA was also inhibited by high levels of p21(Asn-17)Ha-ras. However, lower levels of p21(Asn-17) expression were sufficient to block neuronal differentiation without inhibiting induction of these early-response genes. Induction of the secondary-response genes SCG10 and transin by NGF, like morphological differentiation, was inhibited by low levels of p21(Asn-17) whether or not induction of early-response genes was blocked. Therefore, although inhibition of ras function can inhibit early-response gene induction, this is not required to block morphological differentiation or secondary-response gene expression. These results suggest that ras proteins are involved in at least two different pathways of signal transduction from the NGF receptor, which can be distinguished by differential sensitivity to p21(Asn-17)Ha-ras. In addition, ras and protein kinase C can apparently induce early-response gene expression by independent pathways in PC12 cells.

scholarly journals Altered transcriptional activity of c-fos promoter plasmids in v-raf-transformed NIH 3T3 cells.

1990 ◽  
Vol 10 (11) ◽  
pp. 6073-6078 ◽  
Author(s):  
Z Siegfried ◽  
E B Ziff
Keyword(s):  
Cell Growth ◽  
Transcriptional Activity ◽  
Early Response ◽  
Regulatory Elements ◽  
3T3 Cells ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Untransformed Control ◽  
Early Response Genes ◽  
Nih 3T3

In cells transformed by v-raf, an oncogenic counterpart of the serine/threonine kinase Raf-1, regulatory elements of the c-fos promoter were active under conditions of cell growth or stimulation for which they were inactive in untransformed control cells. This suggests that v-raf transforms by deregulating transcription of early response genes.

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