Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the effects of ouabain and some specific signal pathway inhibitors on growth regulation in various kinds of leukemia cell lines and to explore the role of signal pathways participating in proliferation or apoptosis of leukemia cells induced by ouabain. By using MTT, the survival rates of leukemia cell lines were observed after utilizing ouabain and the specific signal pathway inhibitors. The expressions of Na(+), K(+)-ATPase alpha1 subunit of leukemia cells were evaluated by RT-PCR and Western blot. The results showed that low concentration of ouabain (10 nmol/L) could increase the survival rates of lymphocytic leukemia Jhhan cell line and megakaryocytic leukemia M07e cell line, and could up-regulate the expression of Na(+), K(+)-ATPase alpha1 subunit. Proliferation of these leukemia cells induced by ouabain could be inhibited by PP2 and PD98059 with different extents. It is concluded that Na(+), K(+)-ATPase plays an important role in signal transductions through binding to CTS (ouabain), and they can activate complex signal pathways regulating the growth of leukemia cells. The proliferation effects of cells promoted by ouabain are mediated by activation of Src kinase and ERK1/2 dependent signaling pathway.
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PMID:[Signal pathways of leukemia cell proliferation induced by ouabain]. 1937 52

Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor (SRF) that promotes the expression of genes associated with cell proliferation, motility, adhesion, and differentiation-processes that also involve dynamic cytoskeletal changes in the cell. MKL1 is inactive when bound to monomeric globular actin (G-actin), but signals that activate the small guanosine triphosphatase RhoA cause actin polymerization and MKL1 dissociation from G-actin. We found a new mechanism of MKL1 activation that is mediated through its binding to filamin A (FLNA), a protein that binds filamentous actin (F-actin). The interaction of FLNA and MKL1 was required for the expression of MKL1 target genes in primary fibroblasts, melanoma, mammary and hepatocellular carcinoma cells. We identified the regions of interaction between MKL1 and FLNA, and cells expressing an MKL1 mutant that was unable to bind FLNA exhibited impaired cell migration and reduced expression of MKL1-SRF target genes. Induction and repression of MKL1-SRF target genes correlated with increased or decreased MKL1-FLNA interaction, respectively. Lysophosphatidic acid-induced RhoA activation in primary human fibroblasts promoted the association of endogenous MKL1 with FLNA, whereas exposure to an actin polymerization inhibitor dissociated MKL1 from FLNA and decreased MKL1-SRF target gene expression in melanoma cells. Thus, FLNA functions as a positive cellular transducer linking actin polymerization to MKL1-SRF activity, counteracting the known repressive complex of MKL1 and monomeric G-actin.
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PMID:Filamin A interacts with the coactivator MKL1 to promote the activity of the transcription factor SRF and cell migration. 2655 16