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1. |
Recombinant Murine Erythropoietin Receptor Expressed in Avian Erythroid Progenitors Mediates Terminal Erythroid DifferentiationIn Vitro |
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Growth Factors,
Volume 10,
Issue 1,
1994,
Page 1-16
SteinleinPeter,
DeinerEva,
LeutzAchim,
BeugHartmut,
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摘要:
AbstractThe biological activity of the recombinant murine erythropoietin receptor (muEpoR) has so far been ascertained only in nonerythroid, established cell lines ectopically expressing the exogenous receptor. Here we show that the regulation of proliferation and differentiation by the muEpoR can be studied in chicken erythroid cells capable of terminal differentiation. The cloned muEpoR was introduced into primary and immortalized chicken erythroblast clones transformed by conditional oncogenes, using retroviral gene transfer. After turning off oncoprotein function, these cells terminally differentiated in response to human erythropoietin (rhu-Epo), similar to cells treated with chicken anemic serum containing avian Epo. Control vector-containing erythroblasts were totally unresponsive to rhu-Epo, but differentiated normally in presence of avian Epo. The avian erythroblasts expressed biologically active muEpoR at physiological levels and bound rhu-Epo with similar high affinity as mammalian erythroblasts expressing endogenous EpoR. Finally, rhu-Epo synergized with insulin in these cells similar to avian Epo. Our results demonstrate that the exogenous muEpoR is able to mediate normal, terminal differentiation in avian erythroid progenitors.
ISSN:0897-7194
DOI:10.3109/08977199409019599
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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2. |
Homodimeric Murine Interleukin-3 Agonists Indicate that Ligand Dimerization is Important for High-Affinity Receptor Complex Formation |
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Growth Factors,
Volume 10,
Issue 1,
1994,
Page 17-27
MütherHorst,
KühlckeKlaus,
GessnerAndré,
AbdallahSaid,
LotherHeinz,
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摘要:
AbstractHomodimeric murine interleukin 3 (mIL-3) agonists were generated by intermolecular cystine-bonding. Steady-state binding assays and association kinetics performed at 4°C using these agonists revealed specific binding to both the high-and low-affinity receptor. DSS-mediated crosslinking studies performed at 4°C with agonist concentrations compatible with high-affinity receptor complex formation allowed to detect protein complexes of theαchain, theβchain(s) and the high-affinity receptor complex migrating with apparent molecular weights of 90 kDa, 140 kDa, and above 180 kDa, respectively. In contrast, monomeric mIL-3 was crosslinked to theαchain receptor only unless high concentrations were used. Binding studies performed at 4°C revealed a positive cooperative interaction of monomeric mIL-3 with the low-affinity receptor. Proliferation studies and association kinetics performed at 37°C showed that under physiological conditions these agonists were at least 2-to 3-fold more potent than monomeric mIL-3. We therefore propose that dimerization of mIL-3 may be involved in high-affinity receptor complex formation.
ISSN:0897-7194
DOI:10.3109/08977199409019600
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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3. |
Basic FGF and IGF-I Promote Differentiation of Human SH-SY5Y Neuroblastoma Cells in Culture |
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Growth Factors,
Volume 10,
Issue 1,
1994,
Page 29-39
LaveniusErik,
ParrowVendela,
NånbergEewa,
PåhlmanSven,
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摘要:
AbstractPhorbolester-triggered differentiation of SH-SY5Y neuroblastoma cells requires serum and a prolonged activation of protein kinase C (PKC). Under serum-free conditions development of a mature phenotype requires phorbolester in combination with a member of either the insulin-like growth factor (IGF) or the platelet-derived growth factor family. Here we report that basic and acidic fibroblast growth factor (FGF) and epidermal growth factor, but not nerve growth factor, synergistically potentiate phorbolester-induced differentiation. Alone these factors induced a mitogenic response which varied in magnitude, with basic FGF and IGF-I being the two most potent mitogens. However, a combination of basic FGF and IGF-I induced differentiation as judged by morphology and the increase in growth associated protein (GAP-43) and neuropeptide tyrosine mRNA levels. In contrast to the phenotype obtained in the presence of phorbolester, bFGF and IGF-I-treated SH-SY5Y cells retained their capacity to proliferate. Finally, in these cells, the phosphorylation of the endogenous PKC substrate, myristoylated alanine-rich C-kinase substrate (MARCKS), was slightly increased during several days, suggesting an involvement of PKC in the bFGF and IGF-I-induced differentiation.
ISSN:0897-7194
DOI:10.3109/08977199409019601
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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4. |
Platelet-Derived Growth Factor Induces Phosphatidylinositol 3-Kinase Release from the Middle T-pp60c-srcComplex and Association with the Platelet-Derived Growth Factor Receptor |
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Growth Factors,
Volume 10,
Issue 1,
1994,
Page 41-51
XingQun,
BaldwinGraham S.,
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摘要:
AbstractBoth platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce autogenesis in normal rat kidney (NRK) fibroblasts transformed by the polyoma virus middle T (pmt) oncogene. In unstimulated pmt-NRK cells phosphatidylinositol 3-kinase forms a complex with the middle T protein and pp60c-src. PDGF treatment causes a release of phosphatidylinositol 3-kinase activity from the complex and a simultaneous increase in activity associated with the PDGF receptor. In contrast after treatment with EGF the majority of phosphatidylinositol 3-kinase activity remains associated with the middle T-pp60c-srccomplex. Proliferation of NRK fibroblasts transformed by the v-src oncogene is already maximal, and no further stimulation is observed with either PDGF or EGF. Neither growth factor induces dissociation of the complex between phosphatidylinositol 3-kinase and pp60v-src. These observations suggest that the complex between phosphatidylinositol 3-kinase, the middle T protein and pp60c-srcis dissociable, and that phosphatidylinositol 3-kinase plays different roles in mitogenic signal transduction by the PDGF and EGF receptors.
ISSN:0897-7194
DOI:10.3109/08977199409019602
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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5. |
A Potent Stimulator of Small Intestinal Cell Proliferation Extracted by Simple Diffusion from Intact Irradiated Intestine:In VitroStudies |
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Growth Factors,
Volume 10,
Issue 1,
1994,
Page 53-61
PottenC. S.,
BoothC.,
ChadwickC. A.,
EvansG. S,
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摘要:
AbstractThe epithelium lining the small intestine is one of the most rapidly proliferating body tissues yet it rarely develops cancers. The proliferation, migration and differentiation of the stem cell progeny appears to be under very strict control. After 8 Gyγirradiation the murine epithelium contains surviving stem cells from which the epithelium rapidly and effectively regenerates, presumably in response to stimulatory signals, and then returns to steady state conditions after overshoots in proliferation. Here we describe the isolation and preliminary characterisationin vitroof a potent stimulatory extract obtained by diffusion from intact murine small intestine, post-irradiation.In addition toin vivoresponses the extract stimulates intestinal epithelial lines very effectively, most notably the rat IEC 18 line where it can replace the serum requirement. The extent of the induced increase in proliferation could not be reproduced by any other single growth factor tested. Preliminary evidence suggests the extract contains either a potent stimulatory cocktail of factors or a novel intestinal growth factor(s).
ISSN:0897-7194
DOI:10.3109/08977199409019603
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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6. |
Small Intestinal Growth Regulatory Factors Extracted by Simple Diffusion from Intact Irradiated Intestine and TestedIn Vivo |
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Growth Factors,
Volume 10,
Issue 1,
1994,
Page 63-75
PottenC. S.,
ChadwickC. A.,
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摘要:
AbstractFollowing a dose of 8 Gy ofγ-rays delivered to the entire body of BDF1 mice, the proliferative activity in the crypts of the small intestine changes. The labelling and mitotic activity both fall precipitously, but in the lower regions of the crypt recovery from this fall begins soon after irradiation with cyclic fluctuations. Forty-five to fifty hours after irradiation, control levels are reached after which there is an overshoot. The number of clonogenic cells in the crypt shows a somewhat similar pattern of regeneration and overshoot. It has been assumed that these changes reflect the production of endogenous signals for proliferation and inhibition and these might be extracted by diffusion through the gut wall. We report here that at appropriate times after irradiation stimulatory and inhibitory extracts could be prepared. Appropriatein vivoassay techniques have been developed for testing inhibitors or stimulators making similar use of the patterns of proliferative regeneration after irradiation. Extracts prepared at either 15 h or 39 h after irradiation, i.e. during the phase of active regeneration are quite potently stimulatory on recipient animals 96 h after irradiation (i.e., following the decline from a proliferative overshoot) when injected twice 3 h apart. Extract prepared 72 h after irradiation (shortly after the overshoot peak) is strongly inhibitory when tested on unirradiated animals, or animals 90 h after irradiation, when injected four times 2 h apart. An accompanying paper shows that the stimulatory extract is powerfully active on intestinal cell lines. Thein vitroapproach is currently being used to characterise the stimulatory factor.
ISSN:0897-7194
DOI:10.3109/08977199409019604
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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