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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P19 EPI-7, a differentiated murine embryonal carcinoma cell line with an epithelioid morphology, does not require external growth factors for proliferation under clonal and subconfluent conditions. At saturation density, however, cells become quiescent in the G1/G0 phase of the cell cycle from which they can be restimulated, particularly upon addition of epidermal growth factor. Medium conditioned by confluent P19 EPI-7 cultures is able to enhance clonal outgrowth of this cell line, suggesting that autocrine growth factor loops may be acting in these cells. Analysis of conditioned serum-free medium shows that this cell line produces a platelet-derived growth factor-like growth factor, next to a type beta transforming growth factor and large amounts of insulin-like growth factor II (IGF-II) and an IGF-binding protein with high specificity for IGF-II. This latter observation has been confirmed by the use of a specific bioassay for IGFs, based on their ability to specifically stimulate proliferation of MCF-7 human breast cancer cells. The amount of IGF-II produced (0.5 mg/liter conditioned medium) makes P19 EPI-7 one of the best producing cell lines for this factor described so far. Receptor cross-linking analysis shows that this cell line contains IGF-I receptors, but no specific receptors for IGF-II. Depending on the conditions tested, transforming growth factor-beta 1 either act as a growth-stimulating factor or as a strong growth inhibitory factor. These data demonstrate that upon cellular differentiation, embryonal carcinoma cells can be formed which produce polypeptide growth factors and are also able to respond to such factors. These observations are discussed in the light of the role of autocrine and paracrine growth stimulation processes during early murine development.
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PMID:Production of insulin-like growth factors, platelet-derived growth factor, and transforming growth factors and their role in the density-dependent growth regulation of a differentiated embryonal carcinoma cell line. 253 20

The platelet-derived growth factor (PDGF) family consists of three different dimeric forms, AA, BB, and AB, of the two constituent polypeptide chains, A and B. These interact with two different cell surface receptors that, in part, mediate different cellular functions. The various forms of PDGF, as well as the receptors, are expressed at high frequency in glioblastoma multiforme, and it has been suggested that the growth of this tumor might be affected by autocrine loops involving PDGF and its receptors. The present paper focuses on recent discoveries regarding the family of PDGF ligands and receptors, as well as reviews results concerning PDGF-dependent autocrine growth in experimental and spontaneous glioblastoma.
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PMID:Structural and functional aspects of platelet-derived growth factor and its role in the pathogenesis of glioblastoma. 254 95

The platelet-derived growth factor (PDGF) receptor is a single membrane-spanning polypeptide of 180,000 daltons with a ligand-stimulatable tyrosine kinase site. We have investigated changes in the structure and association state of the receptor that are induced by ligand binding, but which precede autophosphorylation. Chemical cross-linking of PDGF-bound 32P-labeled receptor and 125I-PDGF-labeled receptor resulted in the generation of a radiolabeled cross-linked complex of 370-390 kDa. This band, as well as the 180-190-kDa PDGF receptor band, were recognized by a PDGF receptor-specific antipeptide antibody. The appearance of the 370-390-kDa band was PDGF-dependent and was seen irrespective of whether the receptor was membrane-bound, solubilized, or highly (approximately 90%) purified. Sedimentation analysis of the 125I-PDGF cross-linked receptor showed that both 180-190- and 370-390-kDa labeled species sedimented as a single peak at about 11.5 S, a position expected of a receptor dimer, demonstrating that the liganded receptor exists essentially as a dimer. In contrast, unliganded receptors sedimented as a single species at 7 S, a position consistent with a monomeric structure. The monomer-dimer interconversion was absolutely ligand-dependent and occurred independent of autophosphorylation. These results demonstrate and intimate correlation between PDGF binding and inter-receptor bond formation, and raise the possibility that the phenomenon may be causally linked to the process of kinase activation.
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PMID:Ligand-induced dimerization of the platelet-derived growth factor receptor. Monomer-dimer interconversion occurs independent of receptor phosphorylation. 254 80

Undifferentiated P19 and PC13 murine embryonal carcinoma (EC) cells have been analyzed for their ability to secrete polypeptide growth factors. This has been carried out by a combination of specific bioassays and the use of biochemical and immunological detection methods. Both P19 and PC13 EC cells secrete a platelet-derived growth factor (PDGF)-like growth factor, a type beta transforming growth factor, and insulin-like growth factors. In addition, PC13 EC cells secrete a heparin-binding growth factor functionally related to fibroblast growth factor, while P19 EC cells secrete transforming growth factor-alpha. This is the first demonstration for secretion of transforming growth factor-alpha by an equivalent of early embryonic cells. The possible paracrine growth stimulating effects of these growth factors have been tested on differentiated derivatives of P19 EC cells, corresponding to all three germ layers. The differences in growth factor production by various embryonal carcinoma cells are discussed in relation to the developmental origin of these cell lines.
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PMID:Identification and characterization of polypeptide growth factors secreted by murine embryonal carcinoma cells. 265 Nov 84

Human platelet-derived growth factor (PDGF) is composed of two polypeptide chains, PDGF-1 and PDGF-2, the human homolog of the v-sis oncogene. Deregulation of PDGF-2 expression can confer a growth advantage to cells possessing the cognate receptor and, thus, may contribute to the malignant phenotype. We investigated the regulation of PDGF-2 mRNA expression during megakaryocytic differentiation of K562 cells. Induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) led to a greater than 200-fold increase in PDGF-2 transcript levels in these cells. Induction was dependent on protein synthesis and was not enhanced by cycloheximide exposure. In our initial investigation of the PDGF-2 promoter, a minimal promoter region, which included sequences extending only 42 base pairs upstream of the TATA signal, was found to be as efficient as 4 kilobase pairs upstream of the TATA signal in driving expression of a reporter gene in uninduced K562 cells. We also functionally identified different regulatory sequence elements of the PDGF-2 promoter in TPA-induced K562 cells. One region acted as a transcriptional silencer, while another region was necessary for maximal activity of the promoter in megakaryoblasts. This region was shown to bind nuclear factors and was the target for trans-activation in normal and tumor cells. In one tumor cell line, which expressed high PDGF-2 mRNA levels, the presence of the positive regulatory region resulted in a 30-fold increase in promoter activity. However, the ability of the minimal PDGF-2 promoter to drive reporter gene expression in uninduced K562 cells and normal fibroblasts, which contained no detectable PDGF-2 transcripts, implies the existence of other negative control mechanisms beyond the regulation of promoter activity.
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PMID:Functional identification of regulatory elements within the promoter region of platelet-derived growth factor 2. 265 98

The genes for platelet-derived growth factor (PDGF) A and PDGF B chains are expressed in a variety of biological situations. Active PDGF consists of two distinct but homologous polypeptide chains, PDGF A and PDGF B, which are found as heterodimers or homodimers. We report a novel situation in which there is selective expression of mRNA encoding PDGF B in cell lines derived from baby hamster kidney (BHK) following transfection with various gene/cDNA constructs and following growth selection with methotrexate. The process of transfection itself, and not expression of the proteins encoded by the transfected genes/cDNAs (hormones, enzymes, and structural proteins), induces expression of PDGF B. No PDGF B mRNA is detectable in control cell lines. Low levels of mRNA encoding PDGF A are constitutively present and are not changed by transfection and or growth selection. PDGF-like activity is present in the medium whenever PDGF B mRNA is detected. The composition of the secreted PDGF dimer cannot be established from our data, but quantitative analysis of mRNA suggests that the PDGF is a B-B dimer. However, the data show that transcription of the PDGF A and PDGF B genes in BHK cells is regulated independently, similar to that reported for some human tumor cells. Furthermore, the selective expression of PDGF B in response to the introduction of foreign genes and to growth selection may be an important aspect of the reaction of these cells to nonoptimal growth conditions, allowing survival and growth of the cells that express PDGF B.
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PMID:Selective expression of mRNA encoding platelet-derived growth factor B chain following transfection of foreign genes into cell lines derived from baby hamster kidney. 265 48

The oncogenic retroviruses can be divided into two main categories: those that induce neoplasia after a long latent period (chronic leukemia viruses) and those that induce neoplasia relatively rapidly (acute transforming viruses). Chronic leukemia viruses do not transform cells in tissue culture and contain only the virally encoded genes. By nucleotide sequence comparison, it was possible to show that all retroviruses have a common evolutionary origin. In contrast, acute transforming viruses have substituted viral genes with genetic information specifically implicated in the oncogenic process. These genetic elements (oncogenes) were derived from uninfected host genomes. It was shown that one of the oncogenes, c-sis proto-oncogene, is the structural gene for the B-chain polypeptide of platelet-derived growth factor (PDGF). Furthermore, high level expression of human c-sis resulted in transformation of recipient cells. Similar results have been subsequently obtained for other growth factors, including granulocyte-macrophage colony stimulating factor, transforming growth factor alpha, epidermal growth factor, and basic fibroblast growth factor. It is possible that growth factor gene activation represents one of the steps leading toward malignancy in vivo.
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PMID:Growth factor genes as oncogenes. 266 Aug 38

Interactions of vascular endothelial cells (ECs) and smooth muscle cells (SMCs) were studied by testing the ability of cultured bovine aortic ECs to secrete factors influencing the migration of cultured aortic SMCs from the same species. Migration of SMCs was examined in blind-well chambers using gelatin-coated polycarbonate filters. Conditioned culture medium obtained by incubating confluent monolayers of ECs in serum-free RPMI-1640 medium for 48 hours caused a 2.4-fold increase in the migration of SMCs as compared with nonconditioned medium (p less than 0.001). The effect was dependent on the length of conditioning with the ECs and was chemotactic in nature as judged on the basis of checkerboard analysis. Preliminary characterization of the migration stimulating activity indicates that it is sensitive to trypsin, nondialyzable, and stable at 56 degrees C for 30 min. The activity was abolished by heating to 100 degrees C for 20 min but was not significantly inhibited by protamine sulphate, which suggests that most of the activity was not due to platelet-derived growth factor (PDGF)-like proteins. Our results thus show that ECs secrete polypeptide(s) chemotactic for vascular SMCs. Such interactions between ECs and SMCs in vivo might contribute to the migration of medial SMCs into the intima during atherogenesis.
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PMID:Cultured bovine aortic endothelial cells secrete factor(s) chemotactic for aortic smooth muscle cells. 271 9

Both interleukin-1 (IL-1) and platelet-derived growth factor (PDGF) induce proliferation of cultured fibroblasts and smooth muscle cells. These polypeptide mediators are released by activated macrophages and other cell types in response to injury and are thought to have a role in tissue remodeling and a number of pathologic processes. Analysis of the kinetics of [3H]thymidine incorporation by cultured fibroblasts demonstrated that the response to IL-1 is delayed approximately 8 hours relative to their response to PDGF. IL-1 transiently stimulated expression of the PDGF A-chain gene, with maximum induction after approximately 2 hours. Subsequent synthesis and release of PDGF activity into the medium was detected as early as 4 hours after IL-1 stimulation, and downregulation of the binding site for the PDGF-AA isoform of PDGF followed PDGF-AA secretion. Antibodies to PDGF completely block the mitogenic response to IL-1. Therefore, the mitogenic activity of IL-1 for fibroblasts and smooth muscle cells appears to be indirect and mediated by induction of the PDGF A-chain gene.
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PMID:Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. 278 98

The insulin-like biological activities of serum can now be attributed not only to insulin but also to other structurally related polypeptides (somatomedins or insulin-like growth factors, IGF's). Other polypeptides, like epidermal growth factor-urogastrone (EGF-URO) or platelet-derived growth factor (PDGF) have also been observed to cause "insulin-like" responses in their target cells. The similar biological activities of the polypeptides that are structurally related to insulin (IGF-I, IGF-II) can result either from an activation of their own distinctive receptors (the insulin or IGF-I receptors) or from receptor crossover whereby one polypeptide (e.g., IGF-I) can activate a second receptor system (e.g., the one for insulin). The similarity of cellular responses triggered by the insulin and IGF-I receptors can now be understood in terms of the remarkable similarities between these receptors with regard to their structural, immunologic, and enzymatic (protein tyrosine kinase) properties. Furthermore, the common insulin-like biological activities triggered by other growth factor receptors, like the ones for EGF-URO and PDGF, can now be rationalized in terms of the common protein tyrosine kinase activities and homologous amino acid sequences that these receptors exhibit, along with the receptors for insulin and IGF-I. Although some of the activities of insulin and these growth factors are similar, other actions of these agents are distinct.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Receptors for insulin and other growth factors: rationale for common and distinct mechanisms of cell activation. 282 14


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