Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The v-sis oncogene and its cellular homolog c-sis encode chain B of platelet-derived growth factor. Cells transformed by v-sis produce a platelet-derived growth factor-related molecule which is able to stimulate the platelet-derived growth factor receptor in an autocrine fashion. Site-directed mutagenesis was used to construct several mutations which substitute charged residues for hydrophobic residues in the proposed signal sequence of the v-sis gene product. Two of these mutations resulted in the synthesis of altered v-sis gene products with an unexpected nuclear location and a loss of biological activity. We also report here the intracellular localization of the v-sis gene product to the endoplasmic reticulum-Golgi compartment, where signal sequence cleavage and N-linked glycosylation occur. The v-sis gene product contains no transmembrane regions, as it is completely protected within isolated microsomes from trypsin proteolysis. Site-directed mutagenesis was also used to alter a proposed proteolytic processing site in the v-sis gene product. This mutant v-sis gene, which encodes Asn-Ser in place of Lys-Arg at residues 110 to 111, was found to retain full biological activity.
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PMID:Biosynthesis of the v-sis gene product: signal sequence cleavage, glycosylation, and proteolytic processing. 353 1

Rat mesangial cells (MC) release a factor that competes in a dose-dependent manner with 125I-labeled platelet-derived growth factor (PDGF) for binding to human foreskin fibroblasts (HFF). The competitor activity in mesangial cell conditioned medium (MCCM) is reversible, trypsin sensitive, and inhibited by anti-PDGF IgG. MCCM also expresses potent mitogenic activity to HFF. Anti-PDGF IgG, in concentrations that completely abolished the mitogenic activity of pure PDGF and the competitor activity of MCCM, only partially (33-41%) inhibits this mitogenic activity. The PDGF receptor competing activity as well as the total mitogenic activity, coelutes with labeled pure PDGF on Sephacryl S-200 gel chromatography. Cation exchange chromatography of concentrated MCCM yields a major mitogen peak with little competitor activity and a smaller mitogenic peak with comparable competitor activity, suggestive of the presence of other mitogens in MCCM besides the PDGF-like protein. PDGF is a potent mitogen and may play a role at inflammatory sites. The production of PDGF-like protein by MC may provide insights for understanding the pathogenesis of glomerular diseases.
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PMID:Production of platelet-derived growth factorlike protein by rat mesangial cells in culture. 362 83

The regulation of DNA synthesis in 19 day rat fetal lung epithelial (alveolar type II) and mesenchymal (fibroblast) cells by protein growth factors has been studied. In each case a single growth factor is capable of stimulating 3H-thymidine incorporation into DNA: platelet-derived growth factor in the case of the alveolar type II cell and epidermal growth factor in the case of the fetal lung fibroblast. We hypothesize that these results indicate that the type II cell endogenously produces progression activities (i.e., epidermal growth factor-like and somatomedin-like activity) while the fibroblast produces competence (i.e., platelet-derived growth factor-like) and progression (i.e., somatomedin-like activity). The latter is in keeping with previous observations with skin fibroblasts. To test the above hypothesis, the effect of fetal lung fibroblast-derived conditioned media upon the growth of fetal alveolar type II cells has been determined. The results indicate that, indeed, such media contain competence activity for this cell type. The mitogenic activity was further characterized as heat-sensitive, trypsin-sensitive, and has an apparent molecular weight of 30,000 Daltons. It is not synthesized by 19 day fetal liver, kidney or skin fibroblasts and its synthesis is higher in lung fibroblasts isolated from 19 day fetuses as compared to those isolated on day 16 or day 22.
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PMID:Reciprocal autocrine and paracrine regulation of growth of mesenchymal and alveolar epithelial cells from fetal lung. 378 May 99

A human platelet sonicate was evaluated for its effects on the growth of human metastatic melanoma colony-forming cells in soft agar from cells in culture and from biopsies. The addition of platelet sonicate increased both cloning efficiency and proliferative capacity in that more and larger colonies were formed. In more detailed studies under growth-limiting conditions, melanoma cellular responses to known growth factors were compared to the activity found in the platelet sonicate. None of the growth factors tested either alone or in combination, including platelet-derived growth factor, epidermal growth factor, alpha-type transforming growth factor, and beta-type transforming growth factor, were capable of inducing melanoma colony formation to the 12-fold stimulation observed with the platelet sonicate. Treatment of platelet sonicate with dithiothreitol, trypsin, or acid resulted in loss of activity for human melanoma. Our results suggest that human platelets contain an acid-sensitive protein which can support the expression of the transformed phenotype of human melanoma, and this factor is distinct from acid-stable activities previously characterized from human platelets.
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PMID:Stimulation of human metastatic melanoma colony-forming cells by an acid-sensitive factor in human platelet sonicate. 386 28

In proliferative vitreoretinopathy, retinal pigment epithelial cells and glial cells migrate into the vitreous, proliferate, and assume characteristics of myofibroblasts. The addition of vitreous to the culture media stimulates the proliferation of porcine retinal pigment epithelial cells, bovine and lapine dermal fibroblasts but not the proliferation of bovine aortic endothelial cells and smooth muscle cells. The mitogenic activity is not species-specific, since vitreous from various species stimulates the proliferation of these cells. The mitogenic activity is destroyed by heating at 100 degrees C for 10 min or by trypsin treatment. Since the vitreous, under our assay conditions, was not mitogenic for endothelial cells or smooth muscle cells, the mitogenic activity is probably not derived from leakage into the vitreous of circulating fibroblast, epidermal or platelet-derived growth factor.
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PMID:Vitreous stimulates proliferation of fibroblasts and retinal pigment epithelial cells. 409 53

Incubation of quiescent chicken embryo cells with platelet-derived growth factor, epidermal growth factor, or serum was found to stimulate phosphorylation of two proteins of ca. 42,000 daltons on tyrosine. These proteins are structurally related to each other and to two proteins phosphorylated on tyrosine under similar conditions in mitogen-treated mouse fibroblasts. Three other very different mitogenic agents, the protease trypsin and the chemically unrelated tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate and teleocidin, stimulated phosphorylation of the same proteins. In all cases, phosphotyrosine was detected in these phosphoproteins. Although additional changes in protein phosphorylation were evident, no other proteins were observed by two-dimensional gel electrophoresis which contained increased amounts of phosphotyrosine in mitogen-treated chicken embryo cells. One of these 42,000-dalton proteins was shown previously to be phosphorylated on tyrosine in chicken embryo cells transformed with various retroviruses whose transforming proteins possess tyrosine protein kinase activity. Phosphorylation of the 42,000-dalton proteins could be important in the regulation of cell division.
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PMID:Diverse mitogenic agents induce the phosphorylation of two related 42,000-dalton proteins on tyrosine in quiescent chick cells. 619 61

Two homobifunctional cross-linking reagents have been used to cross-link 125I-platelet-derived growth factor (PDGF) to a cell surface component with an approximate Mr = 164,000 that has many characteristics of a specific PDGF receptor. Excess unlabeled PDGF competed for labeling of this component, while high concentrations of fibroblast growth factor, insulin, epidermal growth factor, low density lipoprotein or acetylated low density lipoprotein had no effect. Preincubation of cells with 125I-PDGF at 37 degrees C reduced specific 125I-PDGF binding (down regulation) and produced a parallel decrease in the amount of the 164,000-dalton receptor available for labeling. The 164,000-dalton component contains at least some protein that is accessible to trypsin in the extracellular medium. A complex of comparable Mr is seen on all PDGF-responsive cell types examined, but not on a nonresponsive cell type. 125I-PDGF does not become covalently cross-linked to this component in the absence of a cross-linking reagent.
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PMID:Platelet-derived growth factor. III. Identification of a platelet-derived growth factor receptor by affinity labeling. 627 60

The platelet-derived growth factor (PDGF) binds specifically to high-affinity receptors on the surface of bovine aortic smooth muscle cells and 3T3 cells. Conditioned medium from cultured bovine aortic endothelial cells (EC) prevents PDGF binding to these receptors in a dose-dependent manner at 4 degrees C. The (125)I-labeled PDGF that is displaced by the conditioned medium shows no increase in trichloroacetic acid solubility or decrease in binding capability to fresh cells. The competitor activity was identified as a protein by ammonium sulfate precipitability and sensitivity to trypsin. The competitor protein also is found in the serum-free conditioned media from porcine aortic EC and human umbilical vein EC but not in media from bovine aortic smooth muscle cells, human neonatal foreskin fibroblasts, or the interleukin-producing thyoma cell line EL-4. The competitor protein, like PDGF, has no effect on the specific 4 degrees C binding of either (125)I-labeled insulin to 3T3 cells or (125)I-labeled epidermal growth factor to human epidermoid A431 cells. Saturation curves of PDGF binding to smooth muscle cells that had been preincubated in the presence and absence of competitor indicate that the concentration for half-maximal binding of (125)I-labeled PDGF to its receptor ( approximately 30 pM) is unchanged by the competitor, whereas the apparent number of available receptor sites or maximal level of binding is greatly diminished. The competitor activity produced by cultured human umbilical vein EC is completely inhibited by antiserum against pure human PDGF, whereas the same PDGF antiserum only partially inhibits the mitogenic activity of the conditioned media. In addition, approximately 7-fold more crude endothelium-derived growth factor is required for half-maximal inhibition of (125)I-labeled PDGF binding as is required for half-maximal stimulation of DNA synthesis. These results suggest that EC secrete a PDGF-like protein that is biochemically distinct from the majority of EC-derived mitogenic activity.
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PMID:Cultured endothelial cells produce a platelet-derived growth factor-like protein. 630 Aug 79

Endothelial cell-derived growth factor (ECDGF) is a soluble mitogen secreted in vitro by bovine aortic endothelium. ECDGF is a mixture of at least two distinct heat-stable and trypsin-sensitive mitogens. Large amounts of mitogenic activity were found in lysates prepared from cultured endothelial cells. Other nonmitogen-secreting cells in culture, including bovine dermal fibroblasts and vascular smooth muscle cells, also contained a similar activity. In contrast to ECDGF, the lysate mitogenic activities were sensitive to heat (56 degrees C) and were not inactivated by trypsin. Similar to platelet-derived growth factor (PDGF), ECDGF and cell lysate mitogens promoted cell proliferation in the absence of other defined mitogens when added to culture medium and after exposure to plastic. The cytoplasmic mitogens, however, were distinct from PDGF by receptor competition assays and other criteria.
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PMID:Comparison of intracellular and extracellular mitogenic activity. 638 30

Adult rat hepatocytes in primary cultures are stimulated to synthesize DNA in response to rat serum, whereas rat plasma is considerably less active. Biological activity is present in rat platelets and is secreted during aggregation in response to thrombin. The material secreted by rat platelets is heat labile and is sensitive to digestion with trypsin, suggesting that it is a protein. When assayed on 3T3 cells this material also stimulates DNA synthesis; however, the trypsin-sensitive activity is heat stable (100 degrees C, 10 min). These results indicate that rat platelets contain hepatotrophic activities which by virtue of their heat sensitivity are distinct from heat-stable platelet-derived growth factor (PDGF)-like mitogenic activities required by 3T3 cells for growth. It is possible that hepatotrophic platelet factors might be involved in mediating liver regeneration in the rat after partial hepatectomy.
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PMID:Rat platelets contain growth factor(s) distinct from PDGF which stimulate DNA synthesis in primary adult rat hepatocyte cultures. 646 36


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