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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular TTB cells derive from murine Kaposi's sarcoma-like dermal lesions and share several phenotypic features with AIDS-associated KS spindle cells. We have recently reported that fibroblast growth factor-2 (FGF-2) promotes dramatic cytoskeletal and morphological alterations in TTB cells, concomitant with the induction of an autocrine loop for hepatocyte growth factor and a relocalization of the urokinase receptor. Since all these alterations are hallmarks of cell transformation. we attempted to verify whether FGF-2 induces a transformed phenotype in TTB cells. Our results show that FGF-2-treated TTB cells acquire the ability to grow under anchorage-independent conditions. In addition, FGF-2 markedly reduced the levels of thrombospondin-1, an antiangiogenic and tumor suppressor protein, in TTB cells. Therefore, FGF-2 induces KS-like spindle cells to acquire properties characteristic of transformed cells. This suggests that FGF-2 plays a pathogenetic role in KS not only by promoting angiogenesis, but also by conferring a transformed phenotype upon KS cells. In light of previous reports on Tat-induced release of FGF-2 into the extracellular space, our findings may provide an additional mechanism for the observed synergism between Tat and FGF-2 in the pathogenesis of KS.
Mol Cell Biol Res Commun 2000 Oct
PMID:Exogenous fibroblast growth factor-2 induces a transformed phenotype in vascular kaposi's sarcoma-like cells. 1140 12

We compared stimulus-coupling pathways involved in bovine pulmonary artery (PA) and lung microvascular endothelial cell migration evoked by sphingosine-1-phosphate (S1P), a potent bioactive lipid released from activated platelets, and by vascular endothelial growth factor (VEGF), a well-recognized angiogenic factor. S1P-induced endothelial cell migration was maximum at 1 microM (approximately 8-fold increase with PA endothelium) and surpassed the maximal response evoked by either VEGF (10 ng/ml) (approximately 2.5-fold increase) or hepatocyte growth factor (HGF) (approximately 2.5-fold increase). Migration induced by S1P, but not by VEGF, was significantly inhibited by treatment with antisense oligonucleotides directed to Edg-1 and Edg-3 (endothelial differentiation gene) S1P receptors and by G protein modification. These strategies included pretreatment with pertussis toxin, or transfection with mini-genes encoding a betagamma subunit inhibitory peptide of the beta-adrenergic receptor kinase, or an 11-amino-acid peptide that inhibits G(1alpha2) signaling. Various strategies to interrupt Rho family signaling, including C(3) exotoxin, dominant/negative Rho, or the addition of Y27632, a cell-permeable Rho kinase inhibitor, significantly attenuated S1P- but not VEGF-induced migration. Conversely, pharmacologic inhibition of either myosin light chain kinase, src family tyrosine kinases, or phosphatidylinositol-3' kinase reduced basal endothelial cell migration and abolished VEGF-induced endothelial cell migration but did not inhibit the increase in S1P-induced migration. Whereas VEGF and S1P increased both p42/p44 extracellular regulated kinase and p38 mitogen-activated protein (MAP) kinase activities, only p38 MAP kinase inhibition significantly reduced VEGF- and S1P-stimulated migration. These data confirm S1P as a potent endothelial cell chemoattractant through G(1alpha2)-coupled Edg receptors linked to Rho-associated kinase and p38 MAP kinase activation. The divergence in signaling pathways evoked by S1P and VEGF suggests complex and agonist-specific regulation of endothelial cell angiogenic responses.
Am J Respir Cell Mol Biol 2001 Jun
PMID:Differential regulation of sphingosine-1-phosphate- and VEGF-induced endothelial cell chemotaxis. Involvement of G(ialpha2)-linked Rho kinase activity. 1141 36

Receptor tyrosine kinases (RTKs) mediate distinct biological responses by stimulating similar intracellular signaling pathways. Whether the specificity of the response is determined by qualitative or quantitative differences in signaling output is not known. We addressed this question in vivo by replacing the multifunctional docking sites of Met, the receptor for hepatocyte growth factor, with specific binding motifs for phosphatidylinositol-3 kinase, Src tyrosine kinase, or Grb2 (Met(2P), Met(2S), and Met(2G), respectively). All three mutants retained normal signaling through the multiadaptor Gab1, but differentially recruited specific effectors. While Met(2G) mice developed normally, Met(2P) and Met(2S) mice were loss-of-function mutants displaying different phenotypes and rescue of distinct tissues. These data indicate that RTK-mediated activation of specific signaling pathways is required to fulfill cell-specific functions in vivo.
Mol Cell 2001 Jun
PMID:Coupling Met to specific pathways results in distinct developmental outcomes. 1143 Aug 31

Hepatocyte growth factor (scatter factor) (HGF/SF) is a pleiotrophic mediator of epithelial cell motility, morphogenesis, angiogenesis, and tumorigenesis. HGF/SF protects cells against DNA damage by a pathway from its receptor c-Met to phosphatidylinositol 3-kinase (PI3K) to c-Akt, resulting in enhanced DNA repair and decreased apoptosis. We now show that protection against the DNA-damaging agent adriamycin (ADR; topoisomerase IIalpha inhibitor) requires the Grb2-binding site of c-Met, and overexpression of the Grb2-associated binder Gab1 (a multisubstrate adapter required for epithelial morphogenesis) inhibits the ability of HGF/SF to protect MDCK epithelial cells against ADR. In contrast to Gab1 and its homolog Gab2, overexpression of c-Cb1, another multisubstrate adapter that associates with c-Met, did not affect protection. Gab1 blocked the ability of HGF/SF to cause the sustained activation of c-Akt and c-Akt signaling (FKHR phosphorylation). The Gab1 inhibition of sustained c-Akt activation and of cell protection did not require the Gab1 pleckstrin homology or SHP2 phosphatase-binding domain but did require the PI3K-binding domain. HGF/SF protection of parental MDCK cells was blocked by wortmannin, expression of PTEN, and dominant negative mutants of p85 (regulatory subunit of PI3K), Akt, and Pak1; the protection of cells overexpressing Gab1 was restored by wild-type or activated mutants of p85, Akt, and Pak1. These findings suggest that the adapter Gab1 may redirect c-Met signaling through PI3K away from a c-Akt/Pak1 cell survival pathway.
Mol Cell Biol 2001 Aug
PMID:The multisubstrate adapter Gab1 regulates hepatocyte growth factor (scatter factor)-c-Met signaling for cell survival and DNA repair. 1143 54

Smads serve as intracellular mediators of transforming growth factor beta (TGF-beta) signaling. After phosphorylation by activated type I TGF-beta receptors, Smad proteins translocate to the nucleus, where they serve as transcription factors and increase or decrease expression of TGF-beta target genes. Mice lacking one copy each of Smad2 and Smad3 suffered midgestation lethality due to liver hypoplasia and anemia, suggesting essential dosage requirements of TGF-beta signal components. This is likely due to abnormal adhesive properties of the mutant hepatocytes, which may result from a decrease in the level of the beta1-integrin and abnormal processing and localization of E-cadherin. Culture of mutant livers in vitro revealed the existence of a parallel developmental pathway mediated by hepatocyte growth factor (HGF), which could rescue the mutant phenotype independent of Smad activation. These pathways merge at the beta1-integrin, the level of which was increased by HGF in the cultured mutant livers. HGF treatment reversed the defects in cell proliferation and hepatic architecture in the Smad2(+/-); Smad3(+/-) livers.
Mol Cell Biol 2001 Aug
PMID:Smad proteins and hepatocyte growth factor control parallel regulatory pathways that converge on beta1-integrin to promote normal liver development. 1143 67

We have combined hemagglutinating virus of Japan (HVJ; Sendai virus) with liposomes for efficient in vitro and in vivo fusion-mediated gene delivery. The HVJ-liposome was a highly efficient vehicle for the introduction of oligonucleotides into cells in vivo as well as for the transfer of genes <100 kbp without damaging cells. By coupling the Epstein-Barr (EB) virus replicon apparatus with HVJ-liposomes (virosomes), transgene expression was sustained in vitro and in vivo. When we added cationic lipids, the HVJ-cationic liposomes increased gene delivery 100 to 800 times in vitro compared with the conventional anionic virosomes and were also more useful for gene expression in restricted areas of organs and for gene therapy of disseminated cancers. We further discovered that the use of anionic virosomes with a virus-mimicking lipid composition (artificial viral envelope; AVE type) increased transfection efficiency approximately 10 fold in vivo, especially in the heart, liver, kidney, and muscle. Most animal organs were found to be suitable targets for the fusigenic virosomes, and numerous gene therapy strategies using this system were successful in animals. The combination of suicide gene therapy with radiation was very effective for killing hepatomas in a mouse model. Arteriosclerosis obliterans in animal models was cured by the transfer of hepatocyte growth factor.
Mol Urol 2001
PMID:Improvements in gene therapy technologies. 1169 May 54

We examined the expression of hepatocyte growth factor (HGF) mRNA and its receptor, c-met mRNA, in the dorsal root ganglia (DRG) and spinal cord of naive adult rats using in situ hybridization histochemistry (ISHH) and the reverse transcription-polymerase chain reaction (RT-PCR) technique. HGF mRNA was expressed in 25.0% of DRG neurons and 80.5% of HGF mRNA-positive neurons expressed trkA mRNA. In the lumbar spinal cord, c-met mRNA signals were observed in the superficial layer of dorsal horn. These results suggest that the HGF/cMet system may be involved in sensory transmission.
Brain Res Mol Brain Res 2001 Dec 16
PMID:Expression of hepatocyte growth factor in primary sensory neurons of adult rats. 1174 65

Hepatocyte growth factor (HGF) is a pleiotropic growth factor that acts on various epithelial cells. The objectives of this study were to determine whether HGF altered the proliferation and prostaglandin (PG) secretion of bovine endometrial stromal and epithelial cells in vitro. We also observed HGF and HGF receptor (c-met) mRNA expression in cultured bovine endometrial stromal and epithelial cells by RT-PCR. Stromal and epithelial cells obtained from cows in early stage of the estrous cycle (days 2-5) were cultured in DMEM/Ham's F-12 supplemented with 10% calf serum. The cells were exposed to HGF (0-10 ng/ml) for 2, 4, or 6 days. HGF significantly increased the total DNA in epithelial (P < 0.05), but not stromal cells. In another experiment, when the cells reached confluence, the culture medium was replaced with fresh medium with 0.1% BSA containing HGF 0-100 ng/ml and the cells were cultured for 24 hr. The HGF stimulated PGF2alpha secretion in epithelial, but not stromal cells. RT-PCR revealed that mRNA of HGF is expressed only in stromal cells, and that c-met mRNA is expressed in both stromal and epithelial cells. These results suggest that HGF plays roles in the proliferation and the regulation of secretory function of bovine endometrial epithelial cells in a paracrine fashion.
Mol Reprod Dev 2001 Dec
PMID:Expression and action of hepatocyte growth factor in bovine endometrial stromal and epithelial cells in vitro. 1174 58

Hepatocyte growth factor/scatter factor (HGF/SF) induces proliferation, motility and morphogenesis of cells that express the proto-oncogene for the tyrosine kinase receptor, c-Met. Because these cellular events occur in the endometrium during the menstrual cycle and in placenta during development, we have initiated studies of this growth factor in these tissues from macaques. Several HGF/SF alternatively spliced transcripts have been previously reported in other tissues. However, expression of HGF/SF isoforms in the endometrium has not been studied. Here we describe the relative transcript amounts of HGF/SF isoforms in the endometrium and placenta using RNase protection analyses. During these analyses, we discovered two unexpected protected bands that were found through sequence analyses to represent isoforms similar to the previously reported NK1 and NK2 except that they encode a five amino acid deletion in the first kringle domain. We designated these two isoforms as dNK1 and dNK2. Endometrium expressed all of the isoforms; however, dNK2 was consistently expressed at higher levels than NK2 transcripts. In contrast, placenta expressed NK2 and dNK2 mRNA at equal levels, and both NK1 and dNK1 were undetectable in placenta. HGF/SF function in endometrium and placenta may involve complex interactions between the isoforms of HGF/SF and those of c-Met.
Mol Hum Reprod 2002 Jan
PMID:Novel hepatocyte growth factor/scatter factor isoform transcripts in the macaque endometrium and placenta. 1175 73

Secretion of surfactant proteins A and D (SP-A and SP-D) has been difficult to study in vitro because a culture system for maintaining surfactant secretion has been difficult to establish. We evaluated several growth factors, corticosteroids, rat serum, and a fibroblast feeder layer for the ability to produce and maintain a polarized epithelium of type II cells that secretes SP-A and SP-D into the apical medium. Type II cells were plated on a filter insert coated with an extracellular matrix and were cultured at an air-liquid interface. Keratinocyte growth factor (KGF) stimulated type II cell proliferation and secretion of SP-A and SP-D more than fibroblast growth factor-10 (FGF-10), hepatocyte growth factor (HGF), or heparin-binding epidermal-like growth factor (HB-EGF). Cells cultured in the presence of KGF and rat serum with or without fibroblasts had high surfactant protein mRNA levels and exhibited a high level of SP-A and SP-D secretion. Dexamethasone inhibited type II cell proliferation but increased expression of SP-B. In the presence of KGF, rat serum, and dexamethasone, the mRNAs for the surfactant proteins were maintained at high levels. Secretion of SP-A and SP-D was found to be independent of phospholipid secretion.
Am J Physiol Lung Cell Mol Physiol 2002 Feb
PMID:Maintenance of surfactant protein A and D secretion by rat alveolar type II cells in vitro. 1179 29


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