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

Tyrosine kinase growth factor receptors activate MAP kinase by a complex mechanism involving the SH2/3 protein Grb2, the exchange protein Sos, and Ras. The GTP-bound Ras protein binds to the Raf kinase and initiates a protein kinase cascade that leads to MAP kinase activation. Three MAP kinase kinase kinases have been described--c-Raf, c-Mos, and Mekk--that phosphorylate and activate Mek, the MAP kinase kinase. Activated Mek phosphorylates and activates MAP kinase. Subsequently, the activated MAP kinase translocates into the nucleus where many of the physiological targets of the MAP kinase signal transduction pathway are located. These substrates include transcription factors that are regulated by MAP kinase phosphorylation (e.g., Elk-1, c-Myc, c-Jun, c-Fos, and C/EBP beta). Thus the MAP kinase pathway represents a significant mechanism of signal transduction by growth factor receptors from the cell surface to the nucleus that results in the regulation of gene expression. Three MAP kinase homologs have been identified in the rat: Erk1, Erk2, and Erk3. Human MAP kinases that are similar to the rat Erk kinases have also been identified by molecular cloning. The human Erk1 protein kinase has been shown to be widely expressed as a 44-kDa protein in many tissues. The human Erk2 protein kinase is a 41-kDa protein that is expressed ubiquitously. In contrast, a human Erk3-related protein kinase has been found to be expressed at a high level only in heart muscle and brain. The loci of these MAP kinase genes are widely distributed within the human genome: erk2 at 22q11.2; erk1 at 16p11.2; and ek3-related at 18q12-21. In the yeast Saccharomyces cerevisiae, five MAP kinase gene homologs have been described: smkl, mpk1, hog1, fus3, and kss1. Together, these kinases are a more diverse group than the human erks that have been identified. Thus the erks are likely to represent only one subgroup of a larger human MAP kinase gene family. A candidate for this extended family of MAP kinases is the c-Jun NH2-terminal kinase (Jnk), which binds to and phosphorylates the transcription factor c-Jun at the activating sites Ser-63 and Ser-73. Evidence is presented here to demonstrate that Jnk is a distant relative of the MAP kinase group that is activated by dual phosphorylation at Tyr and Thr.
Mol Reprod Dev 1995 Dec
PMID:Transcriptional regulation by MAP kinases. 860 77

The dopamine receptor antagonist, haloperidol, produced a time-dependent differential induction of inducible transcription factors (ITFs) in rat striatal neurons: Fos, Fos B, Jun B, Jun D, Krox 20, and Krox 24, but not c-Jun, were induced in the caudate putamen and nucleus accumbens with varying time courses. The induction of Fos by haloperidol was stronger in anterior versus posterior regions of the striatum. In contrast, induction of Fos by the muscarinic agonist pilocarpine was stronger in the posterior regions of the striatum suggesting that muscarinic receptors do not play a role in the induction of ITFs in striatal neurons by haloperidol. Although c-Jun was not induced in caudate neurons by haloperidol it was strongly induced in these neurons following prolonged seizure activity. The differential pattern of Jun protein expression suggests that haloperidol induces a specific transcriptional program in basal ganglia neurons. These effects of haloperidol may be involved in producing its extrapyramidal side effects.
Brain Res Mol Brain Res 1995 Dec 28
PMID:Differential expression of inducible transcription factors in basal ganglia neurons. 875 Aug 32

Previous studies have shown that ionizing radiation-induced cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. In the present study, we have observed c-Jun induction in cells sensitive to ionizing radiation during the whole process of radiation-induced cell death, and that this expression is accompanied by modifications in the composition of AP-1 complexes: c-Jun/AP-1 activity is highly increased whereas Jun D/AP-1 is slightly decreased. These results show that c-Jun expression and c-Jun/AP-1 activity are induced in the developing brain following ionizing radiation.
Neurosci Lett 1995 Dec 29
PMID:Ionizing radiation-induced apoptosis is associated with c-Jun expression and c-Jun/AP-1 activation in the developing cerebellum of the rat. 878 42

Chromaffin cells of the adrenal medulla are neural crest-derived neuroendocrine cells that express neuropeptide genes in vivo and in vitro. As such these cells are useful for examining tissue- and cell-specific regulation of the enkephalin gene. We previously demonstrated that the chromatin configuration of the enkephalin gene correlated with its tissue-specific expression in the adrenal medulla and primary chromaffin cell cultures. In this study we examine and characterize binding of transcription factors to the enkephalin promoter/enhancer region. Gel shift analyses of this region with extracts from chromaffin cells and PC12 cells (a pheochromocytoma cell line that does not express the enkephalin gene) demonstrate that all detectable binding is to ENKCRE-2, a cyclic AMP response-like element, and that the binding is cell specific. Gel shift and supershift analyses show that, unlike reports demonstrating that binding activity in the CNS is composed of the cyclic AMP response element binding protein, CREB, the majority of protein binding in chromaffin cells is from the AP-1 family of transcription factors. This binding is composed of c-Jun, JunD, and possibly a novel Fos-related protein(s). These data suggest enkephalin gene expression in the adrenal gland is controlled by cell-specific binding of transcription factors from the Fos/Jun families to the enkephalin CRE-2 element. Furthermore, these data suggest at least two different modes of enkephalin gene regulation exist between endocrine and neuronal tissues.
J Neurochem 1996 Dec
PMID:AP-1-related proteins bind to the enkephalin CRE-2 element in adrenal chromaffin cells. 893 56

The alpha subunit gene encodes a common subunit shared by all glycoprotein hormones. This single copy gene is expressed in pituitary gonadotropes and thyrotropes of all mammals and in placental trophoblasts of primates and horses. Tandem cAMP response elements (CREs) in the promoter of the human gene are key mediators of this pattern of cell-specific expression. Replacing the palindromic CREs with non-primate variant CREs significantly attenuated activity in trophoblasts but not in gonadotropes. Furthermore, proteins binding the palindromic CRE cross-reacted with antibodies for CREB, CREM, ATF1, ATF2, and c-Jun, while proteins binding the variant CRE cross-reacted only with ATF2 and c-Jun antibodies. The data suggest that ATF2 and c-Jun can activate transcription through the CREs in gonadotropes but not in trophoblasts. Additional analyses indicated that while promoters with either palindromic or variant CREs have similar overall activity in gonadotropes, the variant CREs make a much smaller contribution to promoter activity than their palindromic counterparts. The weaker contribution of the variant CREs is compensated by the activity of two upstream elements present in the promoter. This compensation probably occurs through an indirect mechanism, as the binding affinity of proteins to the CRE is not influenced by the presence of these upstream elements.
J Biol Chem 1996 Dec 06
PMID:The cAMP response elements of the alpha subunit gene bind similar proteins in trophoblasts and gonadotropes but have distinct functional sequence requirements. 894 Jan 85

Prostaglandin synthase 2 (PGS2) is an immediate-early gene induced in a variety of cellular contexts. We investigate here the transcriptional activation of the murine PGS2 gene in NIH 3T3 cells, in response to the mitogens platelet-derived growth factor (PDGF) or serum. Site-directed mutagenesis experiments demonstrate that a consensus cyclic AMP response element (CRE) in the murine PGS2 promoter is essential for optimal PGS2 gene expression in response to PDGF or to serum. Overexpression of c-Jun potentiates PDGF- or serum-induced luciferase expression from a reporter construct containing the first 371 nucleotides of the PGS2 promoter. In contrast, overexpression of other transcription factors binding to the CRE element of the PGS2 gene inhibits induction by PDGF or serum. Moreover, positioning the c-Jun activation domain next to the minimal PGS2 promoter via a GAL4 DNA binding site rather than the CRE is sufficient to permit serum or PDGF stimulation of luciferase expression from this modified reporter construct. PDGF or serum treatment both activate c-Jun N-terminal kinase (JNK), the mitogen-activated protein kinase responsible for phosphorylation and activation of c-Jun. Cotransfection of plasmids expressing dominant-negative Ras, Rac1, MEKK-1, or JNK along with the [PGS2][luciferase] reporter prevents induction by PDGF or serum, demonstrating that serum and PDGF induction of the PGS2 gene in NIH 3T3 cells requires activation of a Ras/Rac1/MEKK-1/JNK kinase/JNK signal transduction leading to phosphorylation of c-Jun. Additional cotransfection experiments with plasmids expressing dominant-negative Raf1 and ERK demonstrate that induction of PGS2 gene expression by PDGF and serum also requires activation of a Ras/Raf1/mitogen-activated protein kinase kinase (MAPKK)/ERK signal transduction pathway.
J Biol Chem 1996 Dec 06
PMID:Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet-derived growth factor and serum. 894 Jan 99

Employing immunohistochemistry and in situ hybridization, we studied the temporal and cell type specific localization of c-Fos and c-Jun proteins and the corresponding messenger RNAs (mRNAs) elicited by a single 17beta-estradiol (E2) injection in the uteri of castrated adult mice. Cellular expression of mRNAs was in parallel with the synthesis of proteins within 1 h. E2 stimulated the c-fos expression rapidly and transiently in the epithelium and vascular endothelium. A second small peak of c-Fos protein and c-fos mRNA expression occurred around 11-13 h in the epithelium. No detectable amount of c-fos transcript and protein was present throughout the time course (0-24 h) in the stromal and myometrial cells. E2 treatment caused differential c-jun expression in all uterine cell types. In the epithelium, c-jun mRNA and protein expression was decreased during 1-6 h post injection, and thereafter returned showing small peak around 11-13 h. Induction of c-Jun protein and c-jun mRNA was evident in the stromal and myometrial cells at 2-3 h, and then the expression gradually decreased and returned to nearly control level by 24 h. E2 treatment induced rapid and transient activation of c-jun in the vascular endothelium. Present results suggest that transient increase of c-Fos and decrease of c-Jun protein at the early phase and coexpression of these proteins at the late phase contribute the proliferation of endometrial epithelium in mature mice. Furthermore, c-Fos and c-Jun expression in the vascular endothelium at the early phase may participate in the uterine imbibition.
Endocrinology 1996 Dec
PMID:Temporal and cell-type specific expression of c-fos and c-jun protooncogenes in the mouse uterus after estrogen stimulation. 894 Mar 73

c-Jun N-terminal kinases (JNKs) participate in cellular responses to mitogenic stimuli, environmental stresses, and apoptotic agents. The mechanisms by which JNK integrates with other signaling pathways and regulates the diverse cellular events are unclear. We found JNK, but not p38-mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase 2, to be persistently activated in apoptosis induced by gamma radiation, UV-C, and anti-Fas treatment. Direct correlation was found between JNK activation and apoptosis induced by UV-C and gamma radiation; however, JNK induction and apoptosis induced by Fas signaling were not well correlated. Overexpression of activated JNK1 caused cell death in transfected cells, and the expression of a dominant-negative mutant of MAPK kinase 1 or JNK1 (but not a dominant-negative mutant of p38-MAPK or c-Raf) prevented the UV-C- and gamma radiation-induced cell death. The inductions of JNK in T-cell activation and apoptosis were distinguished by the different activation patterns, transient versus persistent, respectively. Co-treatment with a tyrosine phosphatase inhibitor (sodium orthovanadate) and T-cell activation signals (phorbol 12-myristate 13-acetate plus ionomycin) prolonged JNK induction, followed by T-cell apoptosis. Our data revealed the requirement of the JNK pathway in radiation-induced apoptosis and implicated the importance of the duration of JNK activation in determining the cell fates.
J Biol Chem 1996 Dec 13
PMID:The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. 894 38

Leukocytes adhere to target cells through their integrins and play a crucial role in self-defense, inflammation, and differentiation. Intercellular adhesion molecule-1 (ICAM-1; CD54) is a representative ligand for integrins and is expressed on many cell types, some of which are targets for leukocyte adhesion. Recent studies suggest that adhesion molecules function not only as a cellular glue, but also as a signal transducer. However, it remains to be clearly defined whether engagement of ICAM-1 is able to induce activation signals in target cells. In rheumatoid synovium, synovial cells are known to express abundant ICAM-1 and produce multiple inflammatory cytokines, such as IL-1beta. In this study, we provide the first evidence that ICAM-1 engagement induces activation of the transcription factor AP-1 and transcription of the IL-1beta gene using a specific Ab to cross-link ICAM-1 on a rheumatoid synovial cell line (E11 cells). This evidence includes ICAM-1 cross-linking-dependent induction of 1) in situ IL-1beta transcription and protein synthesis, 2) transiently transfected chloramphenicol acetyltransferase (CAT) reporter plasmids containing both the IL-1beta LPS-responsive enhancer (between -3134 and -2729) as well as multiple copies of an AP-1 site from this enhancer (between -3117 and -3111), and 3) the binding of a Jun/Fos family complex to this AP-1 site. Thus, ICAM-1 not only functions as a glue for integrin binding, but also as a transducer for AP-1 activation signals important for IL-1beta gene transcription.
J Immunol 1996 Dec 01
PMID:Cross-linking of intercellular adhesion molecule 1 (CD54) induces AP-1 activation and IL-1beta transcription. 894 19

When quiescent cells are perturbed, mRNAs encoding proteins that regulate gene transcription and the cell cycle are expressed at higher level. Jun and Fos are examples of proteins that mediate mitogenic signals and influence differentiation. In neurons, axon interruption (axotomy) increases the content of actin, tubulin, Jun D, and c-Jun proteins in association with increases in actin mRNA levels. Jun D protein binds to gene promoter regions, and its expression has been linked to several aspects of cell differentiation. Because Jun D and beta-actin messages have been described as "constitutive" in expression, we wanted to know whether these messages were responsive to axotomizing lesions of the sciatic motor nerve. We crushed the right sciatic nerve in Sprague-Dawley rats and extracted mRNA from the half spinal cord that serves each leg. At 4 days, Northern blots showed a 2.3-fold increase in beta-actin mRNA and a 2.5-fold increase in Jun D mRNA in the right hemicord. In situ hybridization showed either an undiminished or increased concentration of both mRNAs in motor neurons ipsilateral to the lesion at 4 days, even though many had enlarged two-to threefold. By introducing Fluoro-Ruby at the axotomy site, we were able to show that only the axotomized neurons have enlarged. We conclude that aspects of axonal regeneration resemble the embryonic program for neuronal differentiation and are reinitiated by axotomy.
J Neurobiol 1996 Dec
PMID:Axonal regrowth upregulates beta-actin and Jun D mRNA expression. 895 Nov 5


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