Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The BAC-1.2F5 macrophage cell line depends on CSF-1 for proliferation and survival. Phosphorylation and activation of the RAF-1 kinase are among the early events in CSF-1 signal transduction. To characterize the role of RAF-1 in CSF-1-induced proliferation, we overexpressed oncogenically activated RAF-1, cellular RAF-1 and RAF-1 kinase-defective mutant proteins in BAC-1.2F5 cells. We were unable to establish stable cell lines expressing either kinase-negative or full length RAF-1 proteins, implying that expression of these molecules is not tolerated in BAC-1.2F5 cells. Oncogenically activated RAF-1 induces CSF-1-independent growth in the absence of autocrine growth factor production. Autonomous growth is not associated with dedifferentiation, since v-raf-expressing macrophages perform the same immunological functions as control cells. Intriguingly, autonomous growth correlates with the suppression of CSF-1-mediated MAP-Kinase activation and with the low constitutive expression of a number of CSF-1-inducible genes, including fos, jun, ets2, and myc, but also the genes for the inflammatory cytokines TNF alpha and IL-1 beta. Many of these genes have AP-1 binding sites in their promoters, and the v-raf-expressing cells contain constitutive AP-1 binding activity. These data indicate that RAF-1, but not MAP-Kinase, is a key component in CSF-1 mitogenic signal transduction, and are consistent with a working hypothesis in which RAF-1 mediates transcriptional activation of genes via AP-1.
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PMID:v-raf confers CSF-1 independent growth to a macrophage cell line and leads to immediate early gene expression without MAP-kinase activation. 824 34

All-trans retinoic acid and 9-cis-retinoic acid stimulate the activity of steroid sulfatase in HL60 acute myeloid leukemia cells in a concentration- and time-dependent manner. Neither of these 'natural retinoids' augmented steroid sulfatase activity in a HL60 sub-line that expresses a dominant-negative retinoic acid receptor alpha (RARalpha). Experiments with synthetic RAR and RXR agonists and antagonists suggest that RARalpha/RXR heterodimers play a role in the retinoid-stimulated increase in steroid sulfatase activity. The retinoid-driven increase in steroid sulfatase activity was attenuated by inhibition of phospholipase D (PLD), but not by inhibitors of phospholipase C. Experiments with inhibitors of protein kinase C (PKC) show that PKCalpha and PKCdelta play an important role in modulating the retinoid-stimulation of steroid sulfatase activity in HL60 cells. Furthermore, we show that pharmacological inhibition of the RAF-1 and ERK MAP kinases blocked the retinoid-stimulated increase in steroid sulfatase activity in HL60 cells and, by contrast, inhibition of the p38-MAP kinase or JNK-MAP kinase had no effect. Pharmacological inhibitors of the phosphatidylinositol 3-kinase, Akt, and PDK-1 also abrogated the retinoid-stimulated increase in steroid sulfatase activity in HL60 cells. These results show that crosstalk between the retinoid-stimulated genomic and non-genomic pathways is necessary to increase steroid sulfatase activity in HL60 cells.
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PMID:Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways. 1617 10

Biglycan, a small leucine rich proteoglycan, is expressed in almost every tissue of the body, mainly in the extracellular matrix of connective tissues. Although there is an increasing amount of data on the biological role of biglycan protein, its function is still poorly understood. We aimed to gather more information about the biological function of biglycan protein in the cardiac tissues, and its role in signal transduction. Therefore, we generated transgenic mice overexpressing the human biglycan protein and analyzed the cardiac protein profile of transgenic offsprings using quantitative real-time (QRT)-PCR and proteomics. QRT-PCR results showed that most members of extracellular matrix were downregulated whereas cadherins, TGF-beta1, and TGF-beta2 were upregulated. Antibody microarrayer experiment revealed that pyk2, RAF-1, Mcl-1, syntrophin, calmodulin, isoforms of NOS protein family (eNOS, nNOS, and iNOS), and synaptotagmin proteins were unambiguously upregulated in the heart of biglycan transgenic mice. In this study we show that biglycan directly or indirectly activates proteins involved in cardiac remodeling (TGF-beta, pyk2), signal transduction (RAF-1, Mcl-1, syntrophin, calmodulin, nNOS p38MAPK and MAP kinases), cardioprotection (NOS family, TGF-beta) and Ca++ signaling (connexin, calmodulin, synaptotagmin). On the basis of the results presented here, we conclude that biglycan is a multifunctional extracellular protein that has a pivotal role in pathological remodeling of cardiac tissue and mediates cardioprotection.
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PMID:Overexpression of biglycan in the heart of transgenic mice: an antibody microarray study. 1726 42

The aim of the present work was to study the immune profiling of prostate epithelial cells by the expression of ASK-1/p38 and Raf-1/ERK MAP Kinases signaling pathways mediated by TRAF-6. Immunohistochemical and Western blot analyses for TRAF-6, ASK-1, MEK-6, p38, Raf-1, MEK-1, ERK-1, ERK-2 and PSA were carried out in 5 samples of normal prostate gland, 24 samples of BPH and 19 samples of PC. Immunoreaction to TRAF-6 was found in the cytoplasm of epithelial cells of BPH and tumor cells of PC samples. For patients with the profile (TRAF-6+), optical densities revealed a weak immunoexpression of ASK-1 in PC compared to BPH patients. Whereas, immunoexpression to Raf-1 was higher in PC than in BPH. According to the expression of ASK-1 and Raf-1, two main profiles were identified: (TRAF-6+, ASK-1+, Raf-1+) and (TRAF-6+, ASK-1+, RAF-1-) in both BPH and PC. In addition, ASK-1/p38 axis expression was increased in BPH. Raf-1/ERK signaling pathway was increased in PC samples. On the other hand, representing of individual signaling protein expression enclosing each of p38 and ERK MAP Kinases according to TRAF-6+ showed a qualitative behavior of ASK61/p38 and Raf-1/ERK signaling pathways and a dynamic expression of PSA associated with immune and inflammatory process. These findings suggest that prostate epithelial cell could able an immune and inflammatory setting.
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PMID:Immune profiling of human prostate epithelial cells determined by expression of p38/TRAF-6/ERK MAP kinases pathways. 2947 59