ISSN:0897-7194    

DOI:10.3109/08977199109000266

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractInsulin-like growth factors (IGF) I and II are chemically-related single-chain peptides with diverse actions on cellular growth and metabolism. This review will focus on recent information pertinent to the biochemical and molecular biological aspects of these peptides. Three areas will be examined: The structure of the two IGF molecules and their precursors will be analyzed; the complicated anatomy of the IGF genes and their mRNAs will be described; and the multiple ways in which the expression of IGF-I and IGF-II can be regulated will be discussed. Gaps in our understanding of these peptides will be highlighted in the context of opportunities for further investigation in this field.

ISSN:0897-7194    

DOI:10.3109/08977199109000267

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractThe insulin-like growth factors (IGFs) are important metabolic and mitogenic factors involved in cell growth and metabolism. IGF-I and -II belong to a family of peptide hormones that include relaxin and insulin, and they share a high degree of structural similarity with proinsulin. They are produced in the liver and multiple other tissues, and are partially growth hormone dependent. These peptides interact with specific high affinity receptors, designated as type I and type II IGF receptors, as well as with the insulin receptor. IGFs have direct effects on somatic growth and on the proliferation of many tissues and cell types, both in vivo and in vitro. IGF-I is currently thought to be the main mediator of the growth promoting actions of human growth hormone and IGFs also have a profound effect on carbohydrate and lipid metabolism, distinct from that of insulin. A recently recognized class of proteins which have high affinity and specificity for the IGFs, the IGF binding proteins (designated as IGFBPs; Ballard et al., 1989; Rosenfeld et al., 1990), have been shown to be involved in modulation of the proliferative and mitogenic effects of IGFs on cells. The molecular mechanisms involved in the interaction of the IGFBPs with the IGFs and their receptors remain unclear, but it is certain that a full understanding of the actions of IGF in vivo will require the characterization of these binding proteins.

ISSN:0897-7194    

DOI:10.3109/08977199109000268

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractCompetitive binding experiments from a number of laboratories showed that IGF receptors are distinct from insulin receptors, and that there are two types of IGF receptors based on their relative affinities for IGF-I and IGF-II and whether or not they bind insulin (reviewed in Rechler and Nissley, 1985). Later, affinity crosslinking experiments provided a physical basis for the two IGF receptor subtypes. The receptor which preferred IGF-II over IGF-I and did not bind insulin, was a large 250 kDa species with no apparent subunit structure (Fig. 1). The receptor which prefered IGF-I over IGF-II and bound insulin with low affinity had a binding sub-unit of 130 kDa after reduction of disulfide bonds. Biosynthetic labeling experiments demonstrated a 95 kDa beta subunit addition to the 130 kDa alpha subunit (Fig. 1). The heterotetrameric IGF-I receptor (a,&was therefore very similar to the insulin receptor, and the case for similarity was increased when the beta subunit was found to be auto-phosphorylated in response to IGF-I. Molecular cloning of the IGF-I receptor confirmed that the IGF-I receptor and the insulin receptor areclosely related structures (Ullrich et al., 1986).

ISSN:0897-7194    

DOI:10.3109/08977199109000269

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractInternalization of epidermal growth factor (EGF) receptors by human A431 epidermoid carcinoma cells was studied at various culture densities. The extent of EGF receptor internalization was measured by quantitation of internalized125I-EGF during incubation at 37°C for 30 min. When cell culture density was below 1×105cells/cm2receptor internalization was active; 30-40% excess moles of ligand over the moles of surface EGF receptors were internalized during this period. However, when culture density increased to above 1.5×105cells/cm receptor internalization became less extensive, as only 30-50% of ligand bound to the cell surface underwent internalization during 30 min incubation. In parallel with this reduction in receptor internalization, the degradation rate of35S-methionine labeled EGF receptors was reduced at a high culture density. In contrast with this regulation of receptor internalization, the affinity of EGF receptors for the ligand increased as culture density increased. The extent of EGF-dependent receptor phosphorylation was found to be constant at all culture densities tested. Thus, the observed low level of receptor internalization at high culture densities was not attributable to lower responsiveness of receptors to EGF. These data suggest the presence of an as yet unidentified cell density-dependent mechanism for regulating receptor internalization in cultured A431 cells.

ISSN:0897-7194    

DOI:10.3109/08977199109000270

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractTransforming growth factor-β1 (TGF-β1 and recombinant platelet-derived growth factor-BB (rPDGF-BB) promoted an extensive, dose-dependent development of fibrous connective tissue when continuously delivered for 8 days by mini-osmotic pumps implanted subcutaneously in adult guinea pigs. Biochemical analyses demonstrated that TGF-β1 and rPDGF-BB stimulated dose-dependent increases in the dry weight, and protein, DNA, collagen, and glycosaminoglycan (GAG) contents of the fibrous connective tissue capsule that enveloped the pumps. The GAG/DNA mass ratio was markedly elevated by TGF-β1, but the collagen/DNA, protein/DNA, and collagen/protein ratios were not significantly increased. In contrast, rPDGF-BB generally decreased these mass ratios. Histological analyses suggested that this was due to the fact that rPDGF-BB induced a very cellular response with a marked influx of neutrophils and fibroblasts. TGF-β1 induced significantly less cellular response, which consisted primarily fibroblasts and macrophages. These results indicated that rPDGF-BB and TGF-β1 induced connective tissue depositionin vivoin a dose-dependent fashion, although the cellular nature of the responses as well as the structural composition of the extracellular matrices were clearly distinguishable between the two growth factors.

ISSN:0897-7194    

DOI:10.3109/08977199109000271

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractGranulocyte-macrophage colony-stimulating factor (GM-CSF) is produced by cells in the placenta, is known to be a growth factor for trophoblast cells in vitro and when injected into pregnant mice at risk for mid-gestation fetal resorption, dramatically lowers the fetal death rate while stimulating placental and fetal growth. We describe here the localization of GM-CSF mRNA expression in murine placenta by in situ hybridization. It is found in small round cells (lymphoid-like) and endothelial cells in the maternal decidua. In addition, GM-CSF transcripts are located in cells of the spongiotrophoblast zone (trophoblast-like cells), but not in the labyrinthine zone. These results indicate that GM-CSF may be influencing the growth and function of the fetal placenta in a paracrine-autocrine manner. These results support earlier observations that link GM-CSF production during pregnancy to decidual T-lymphocytes and further suggest a placental source within the invasive trophoblast.

ISSN:0897-7194    

DOI:10.3109/08977199109000272

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

AbstractOne approach to the problem of growth factor signal transduction is to identify alterations in growth factor-regulated events in mutants possessing an altered proliferative response. This approach was used in a study of the alterations in protein tyrosine phosphorylation in 22 independently-arising autonomous mutants of the CSF-1-dependent mouse macrophage cell line, BACl.2F5. Only 4 of the mutants produced CSF-1 and/or factors that were capable of down-regulating the CSF-1 receptor (CSF-1R), suggesting that the majority were altered in the signal tranduction pathway for proliferation. All of the mutants possessed lower numbers (13-89%) of cell surface CSF-1Rs than wild type cells. With two possible exceptions, the phosphorylation of the anti-phosphotyrosine-reactive cell surface CSF-1 Rs from CSF-1 stimulated cells was directly proportional to cell surface CSF-I R number. In the absence of CSF-I, three of the 22 mutants exhibited tyrosine phosphorylation of proteins that was not observed in wild type cells under the same conditions. The results indicate that this approach will be useful in the analysis of the growth factor regulated pathway for cell proliferation.

ISSN:0897-7194    

DOI:10.3109/08977199109000273

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor