Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoic acid induces P19 mouse embryonal carcinoma cells to differentiate to endoderm and increases expression of the heterotrimeric G-protein subunits Galpha12 and Galpha13. Retinoic acid was found to induce differentiation and sustained activation of c-Jun amino-terminal kinase, but not of ERK1,2 or of p38 mitogen-activated protein kinases. Much like retinoic acid, expression of constitutively active forms of Galpha12 and Galpha13 induced differentiation and constitutive activation of c-Jun amino-terminal kinase. Expression of the dominant negative form of c-Jun amino-terminal kinase 1 blocked both the activation of c-Jun amino-terminal kinase and the induction of endodermal differentiation in the presence of retinoic acid. These data implicate c-Jun amino-terminal kinase as a downstream element of activation of Galpha12 or Galpha13 obligate for retinoic acid-induced differentiation.
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PMID:c-Jun amino-terminal kinase is regulated by Galpha12/Galpha13 and obligate for differentiation of P19 embryonal carcinoma cells by retinoic acid. 930 8

Eph family receptor tyrosine kinases signal axonal guidance, neuronal bundling, and angiogenesis; yet the signaling systems that couple these receptors to targeting and cell-cell assembly responses are incompletely defined. Functional links to regulators of cytoskeletal structure are anticipated based on receptor mediated cell-cell aggregation and migratory responses. We used two-hybrid interaction cloning to identify EphB1-interactive proteins. Six independent cDNAs encoding the SH2 domain of the adapter protein, Nck, were recovered in a screen of a murine embryonic library. We mapped the EphB1 subdomain that binds Nck and its Drosophila homologue, DOCK, to the juxtamembrane region. Within this subdomain, Tyr594 was required for Nck binding. In P19 embryonal carcinoma cells, activation of EphB1 (ELK) by its ligand, ephrin-B1/Fc, recruited Nck to native receptor complexes and activated c-Jun kinase (JNK/SAPK). Transient overexpression of mutant EphB1 receptors (Y594F) blocked Nck recruitment to EphB1, attenuated downstream JNK activation, and blocked cell attachment responses. These findings identify Nck as an important intermediary linking EphB1 signaling to JNK.
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PMID:Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase. 943 Jun 61

Lamin A is a major component of the nuclear lamina that is expressed in various types of differentiated cells. We have analysed previously the putative promoter sequences of the gene and shown that the rat lamin A proximal promoter contains two essential motifs, a GC box that can bind to Sp1 and Sp3, and an AP-1 motif that can bind to c-Jun and c-Fos. In this study we have investigated the role of Sp1 and Sp3 in transactivation of the promoter. Functional analysis of the promoter in Drosophila SL2 cells has demonstrated that it is inactive in the absence of Sp proteins. Activation by expression of Sp3 is more pronounced than that by Sp1 although both proteins can bind to the GC box in vitro; activation clearly depends on an intact GC box as deduced from mutant analysis. Promoter activity in SL2 cells also requires an intact AP-1 motif, which can bind to endogenous Drosophila Jun and Fos proteins. Furthermore, overexpression of c-Jun and c-Fos results in fourfold activation of the promoter in PCC-4 embryonal carcinoma cells. Our demonstration that activation of the lamin A proximal promoter is mediated by Sp3 and AP-1 transcription factors affords a basis for further studies on the regulation of this important gene during development and disease.
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PMID:SP3 and AP-1 mediate transcriptional activation of the lamin A proximal promoter. 1143 40

P19 embryonal carcinoma cells are known to differentiate into neurons and glia when treated with relatively high concentrations (>100 nM) of retinoic acid (RA). Concomitant with this RA-induced neural differentiation, we observed an activation of the c-Jun amino-terminal kinase (JNK). JNK was required for the RA-induced neural differentiation, because dominant-negative JNK blocked the differentiation. Studies using protein phosphatase inhibitors and protein kinase inhibitors suggested that both okadaic acid-sensitive protein phosphatase(s) and protein kinase C participate in the RA-induced activation of JNK.
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PMID:Activation of c-Jun amino-terminal kinase is required for retinoic acid-induced neural differentiation of P19 embryonal carcinoma cells. 1151 61

Mitogen-activated protein kinases (MAPKs) have been implicated as regulators of differentiation. The biological effect of MAPK signaling in the nucleus is achieved by signal-responsive transcription factors. Here we have investigated MAPK signaling and activation of AP-1 transcription factors in P19 embryonal carcinoma cells undergoing cardiomyocyte differentiation. We show that aggregation and Me(2)SO treatment, which trigger the differentiation response, result in sustained activation of JNK1, p38, and ERK1/2 MAPKs and acquisition of AP-1 DNA binding activity. The induced AP-1 activity consists of c-Jun, JunD, and Fra-2 proteins and is accompanied with the increased expression of these proteins. JNK is involved in c-Jun phosphorylation, whereas ERK and p38 activities are essential for maximal c-Jun and Fra-2 expression, and AP-1 DNA binding activity. While the inhibition of ERK can partially prevent the formation of beating cardiomyocytes, the activity of p38 is absolutely required for the differentiation. Expression of dominant negative c-Jun(bZIP) in P19 cells can also inhibit the differentiation response. Surprisingly, however, expression of dominant negative SEK or JNK causes an inhibition of P19 cell proliferation. Taken together, the results show that ERK, JNK, p38, and AP-1 are activated in a coordinated and sustained manner, and contribute to proliferation and cardiomyocyte differentiation of P19 cells.
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PMID:Mitogen-activated protein kinases and activator protein 1 are required for proliferation and cardiomyocyte differentiation of P19 embryonal carcinoma cells. 1188 86

While analyzing the role of c-Jun NH(2)-terminal kinase (JNK) in neurogenesis in P19 embryonal carcinoma cells, we noticed that treatment with SP600125, a JNK inhibitor, increased the cell size markedly. SP600125-induced enlargement of P19 cells was time- and dose-dependent. The increased cell size in response to SP600125 was also detected in B6mt-1 embryonic stem cells. SP600125 treatment inhibited cell growth and increased DNA contents, indicating the inhibition of cell proliferation resulting from endoreduplication. Concurrently, the gene expression of p21, a regulator of G2/M arrest as well as G1 arrest, was increased in cells treated with SP600125. The increased cell size in response to SP600125 was detected even in P19 cells treated with colcemide, an inhibitor of cell cycle progression at the metaphase. The present study suggests that treatment with SP600125 progresses the cell cycle, skipping cytokinesis in P19 cells.
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PMID:A JNK inhibitor SP600125 induces defective cytokinesis and enlargement in P19 embryonal carcinoma cells. 1971 43

NADPH oxidase 4 (Nox4) generates reactive oxygen species (ROS) that can modulate cellular phenotype and function in part through the redox modulation of the activity of transcription factors. We demonstrate here the potential of Nox4 to drive cardiomyocyte differentiation in pluripotent embryonal carcinoma cells, and we show that this involves the redox activation of c-Jun. This in turn acts to up-regulate GATA-4 expression, one of the earliest markers of cardiotypic differentiation, through a defined and highly conserved cis-acting motif within the GATA-4 promoter. These data therefore suggest a mechanism whereby ROS act in pluripotential cells in vivo to regulate the initial transcription of critical tissue-restricted determinant(s) of the cardiomyocyte phenotype, including GATA-4. The ROS-dependent activation, mediated by Nox4, of widely expressed redox-regulated transcription factors, such as c-Jun, is fundamental to this process.
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PMID:NADPH oxidase 4 regulates cardiomyocyte differentiation via redox activation of c-Jun protein and the cis-regulation of GATA-4 gene transcription. 2358 92


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