Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A distinct family of endothelial cell mitogens that are homologous to platelet-derived growth factor has recently been identified. Unlike other known endothelial cell mitogens, these vascular endothelial cell growth factors (VEGFs) are secreted and appear to act specifically on endothelial cells. We have purified VEGF 2083-fold to apparent homogeneity from protein-free culture medium conditioned by A-431 human epidermoid carcinoma cells. This A-431-derived VEGF was characterized as a homodimer composed of 22-kDa subunits with an N-terminal sequence that was similar to VEGFs produced by human HL-60 leukemic and U-937 histiocytic lymphoma cells. A-431 VEGF was used to identify specific and saturable binding sites for VEGF on human umbilical vein endothelial cells (HUVEC). By affinity cross-linking, VEGF-binding site complexes of 230, 170, and 125 kDa were detected on HUVEC. VEGF specifically induced the tyrosine phosphorylation of a 190-kDa polypeptide, which was similar in mass to the largest binding site detected by affinity cross-linking.
 ...
PMID:Vascular endothelial cell growth factor (VEGF) produced by A-431 human epidermoid carcinoma cells and identification of VEGF membrane binding sites. 171 6

The differentiation of oligodendrocyte-type 2 astrocyte (O-2A) glial progenitor cells into myelin-forming oligodendrocytes is influenced by several polypeptide growth factors. Exposure of O-2A progenitors to basic fibroblast growth factor (bFGF) promotes their sustained proliferation, blocks their differentiation, and maintains both a high level of platelet-derived growth factor (PDGF) alpha-receptors and PDGF sensitivity. Exposure to PDGF, in contrast, promotes only a limited number of cell divisions prior to their differentiation and triggers progenitor cell migration. In the continued presence of bFGF the cells have a stellate morphology with short processes. Upon addition of PDGF these stellate cells become bipolar with long processes, and on removal of PDGF their morphology reverts back to stellate. Thus the phenotype of O-2A progenitor cells in response to these growth factors is plastic. Our studies suggest that bFGF (or a related ligand) in the CNS may sensitize O-2A progenitors to PDGF and thereby initiate their ability to migrate into white matter tracts prior to the onset of myelination.
 ...
PMID:A role for fibroblast growth factor in oligodendrocyte development. 172 57

Genetic messages for polypeptide growth factors were assessed in human alveolar macrophages, obtained by bronchoalveolar lavage (BAL) from normal subjects (N = 3) and from patients with pneumonia (N = 3), pulmonary lymphoma (N = 3), and idiopathic pulmonary fibrosis (N = 3). Complementary DNAs (cDNAs) were prepared by reverse transcription of the RNA extracted from alveolar macrophages before and after culture on a plastic surface. The cDNAs encoding 10 different growth factors were amplified for electrophoretic analysis by polymerase chain reaction with a pair of 3' and 5' primers specific for each factor. Alveolar macrophages from all normal subjects and patients expressed the messages for interleukin-1 beta and transforming growth factor-beta. Alveolar macrophages from some normal subjects also contained message for insulin-like growth factor-1. Alveolar macrophages from six of nine patients with lung diseases also expressed messages for one or more additional growth factors, including epidermal growth factor, transforming growth factor-alpha, interleukin-1 alpha, and platelet-derived growth factor. The polymerase chain reaction technique thus permits determination of the profile of growth factors contributed to pulmonary reactions by alveolar macrophages, which may be important in pulmonary healing and fibrosis.
 ...
PMID:Polymerase chain reaction amplification of messages for growth factors in cells from human bronchoalveolar lavage fluids. 176 30

Cardiac nonmyocytes, primarily fibroblasts, surround cardiac myocytes in vivo. We examined whether nonmyocytes could modulate myocyte growth by production of one or more growth factors. Cardiac myocyte hypertrophic growth was stimulated in cultures with increasing numbers of cardiac nonmyocytes. This effect of nonmyocytes on myocyte size was reproduced by serum-free medium conditioned by the cardiac nonmyocytes. The majority of the nonmyocyte-derived myocyte growth-promoting activity bound to heparin-Sepharose and was eluted with 0.75 M NaCl. Several known polypeptide growth factors found recently in cardiac tissue, namely acidic fibroblast growth factor (aFGF), basic FGF (bFGF), platelet-derived growth factor (PDGF), tumor necrosis factor alpha (TNF alpha), and transforming growth factor beta 1 (TGF beta 1), also caused hypertrophy of cardiac myocytes in a dose-dependent manner. However, the nonmyocyte-derived growth factor (tentatively named NMDGF) could be distinguished from these other growth factors by different heparin-Sepharose binding profiles (TNF alpha, aFGF, bFGF, and TGF beta 1) by neutralizing growth factor-specific antisera (PDGF, TNF alpha, aFGF, bFGF, and TGF beta 1), by the failure of NMDGF to stimulate phosphatidylinositol hydrolysis (PDGF and TGF beta 1), and, finally, by the apparent molecular weight of NMDGF (45-50 kDa). This nonmyocyte-derived heparin-binding growth factor may represent a novel paracrine growth mechanism in myocardium.
 ...
PMID:A growth factor for cardiac myocytes is produced by cardiac nonmyocytes. 180 25

The finding that osteoblasts synthesize collagenase has led to the hypothesis that bone cells play a major role in bone resorption by degrading the surface osteoid layer, thereby preparing the underlying mineralized bone for osteoclastic action. To further understand the mechanisms regulating osteoid removal, mouse calvarial osteoblasts were cultured on 14C-labelled type I collagen films and the abilities of (i) bovine bone matrix extracts and (ii) purified or recombinant human growth factors, to modify their collagenolytic behaviour were investigated. EDTA/Tris-HCl extracts of bone matrix containing growth factor activity, exerted a dose-dependent inhibition of type I collagenolysis by osteoblasts stimulated with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, 10 ng/ml). Inhibition was accompanied by a reduction in collagenase activity and an increase in free TIMP (tissue inhibitor of metalloproteinases) in the culture medium. Transforming growth factor-beta, epidermal growth factor, platelet-derived growth factor and the acidic and basic fibroblast growth factors all mimicked these effects. In contrast, insulin-like growth factors-I and -II did not inhibit type I collagenolysis, only partially inhibited collagenase activity, and did not stimulate TIMP production by either 1,25(OH)2D3-treated or untreated cells. These findings provide additional evidence for the tight control exerted on the proteolytic activity of osteoblasts and the importance of TIMP in its regulation. They suggest strongly that the conversion (coupling) of the initial resorptive phase of the bone remodelling cycle to one of deposition, may be mediated by polypeptide growth factors either produced locally by osteoblasts, or released by proteolysis from the bone matrix.
 ...
PMID:Bone-derived growth factors modulate collagenase and TIMP (tissue inhibitor of metalloproteinases) activity and type I collagen degradation by mouse calvarial osteoblasts. 184 30

Cell surface antigens, the expression of which is highly enhanced along with the transformation of cells, were analyzed. W14 and W31, EJ-ras oncogene-induced transformants of a WKA rat fetus-derived fibroblast WFB, strongly expressed several transformation-associated antigens as defined by monoclonal antibodies 109, 061, and 081. These monoclonal antibodies recognized Mr 86,000, 62,000, and 101,000 molecules, each composed of a single polypeptide chain. The expression of these transformation-associated antigens was negligible on parental WFB cells. Transforming growth factor-beta could enhance the expression of all of these transformation-associated antigens, but platelet-derived growth factor could only enhance the Mr 86,000 kd molecule expression. In the cytotoxicity assays, poly-I:C-induced rat splenic NK cells were cytotoxic to W14 and W31, but not to WFB. The data also showed that the cytotoxicity by these NK cells against NK-sensitive YAC-1 cells was absorbed with the addition of W14, W31, platelet-derived growth factor, or transforming growth factor-beta-stimulated WFB cells. This indicates that NK cells may recognize common target antigens that are expressed among these target cells. It was also indicated that Mr 86,000 and 62,000 molecules were strongly involved in this cytotoxicity, possibly as the target antigens, since F(ab')2 fragments of monoclonal antibodies 109 and 061 strongly inhibited the cytotoxicity. The addition of monoclonal antibody 109, but not 061, inhibited the cytotoxicity even at 60 min after mixing with the effector and target cells, suggesting that the Mr 86,000 molecule may participate in the lethal hit phase of cytotoxicity by NK cells. These data may indicate that some, but not all, transformation-associated antigens are virtually important in the antitumor surveillance mechanisms by the host effector cells, such as NK cells.
 ...
PMID:Natural killer target molecules associated with the transformation of the oncogene-transfected fibroblast. 186 45

Human melanoma cells in culture are the source of a wide variety of polypeptide growth factors. Melanoma-derived basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A and PDGF-B chains, transforming growth factor (TGF)-alpha and TGF-beta, interleukin (IL)-1 alpha and IL-1 beta, and melanoma growth stimulatory activity (MGSA) have similar biochemical and functional properties when compared to their counterparts produced by untransformed cells. In contrast to melanoma cells, normal melanocytes, even under optimal growth conditions, express only TGF-beta 1 and MGSA at detectable levels suggesting that production of the other growth factors is a tumor-associated phenomenon. Recent evidence suggests that at least two of the growth factors, bFGF and MGSA, contribute to autocrine growth stimulation of melanoma cells. Whether PDGF, TGF-alpha, IL-1, and TGF-beta act in an autocrine mode is unclear at present. However, these four growth factors are among those secreted by melanoma cells and, therefore, can be expected to interact with normal cells of the tumor stroma in vivo. Such paracrine effects include not only growth modulation in the context of angiogenesis and stroma formation, but also tissue degradation by proteolytic enzymes, the modification of extracellular matrix composition, and expression of adhesion receptors.
 ...
PMID:Growth factors in melanoma. 187 58

The autocrine, paracrine, or systemic growth factors responsible for fetal lung cell growth are not completely defined. The progression-type insulin-like growth factors and epidermal growth factor, or transforming growth factor-alpha acting through the epidermal growth factor receptor, appear to act on the developing lung epithelium. The competence factors that facilitate the actions of progression factors during lung growth are unknown. Fetal rat lung cells in vitro synthesize a platelet-derived growth factor (PDGF)-like polypeptide, which we have hypothesized may play a paracrine role in normal lung development. Slot blot and Northern blot analyses of fetal rat lung mRNA have been used to determine if there is a relationship between expression of message for PDGF-A or PDGF-B chains, or their cognate receptors, and periods of maximal growth during late fetal rat lung development. Whole lung mRNA was extracted on 18, 19, 20, 21, and 22 days of gestation (term = 22 days). The peak of DNA synthesis, as assessed by expression of message for DNA polymerase alpha, histone 3, and the proto-oncogenes c-fos and c-myc, which are stimulated by binding of growth factors including PDGF, occurred during the canalicular stage of lung development on days 19 and 20 of gestation. Expression of message for PDGF-A and PDGF-B chains was low during the pseudoglandular stage on day 18, peaked during the canalicular stage on days 19 and 20, then fell again during the saccular stage at days 21 and 22 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Platelet-derived growth factor and growth-related genes in rat lung. I. Developmental expression. 191 Aug 22

We have previously shown that BDS.1 rat hepatoma cells are hypersensitive to the antiproliferative effects of glucocorticoids, and secrete a glucocorticoid suppressible mitogenic activity (denoted GSM). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that GSM purified to near homogeneity migrated as a 28-kDa protein under nonreducing conditions and as a single 15-kDa polypeptide in the presence of sulfhydryl reducing agents suggesting a homodimeric structure. Anti-platelet-derived growth factor (PDGF) A-chain specific antibodies selectively immunodepleted the mitogenic activity which can be extracted from nonreducing gels in the 26-30-kDa fraction and, in Western blots, recognized the 15-kDa reduced form of GSM. Western blot analysis further showed that dexamethasone suppressed the level of secreted PDGF A-chain protein in BDS.1 cells but not in glucocorticoid receptor-deficient hepatoma cells. Northern blots revealed that dexamethasone reduced expression of the PDGF A-chain 2.3- and 1.7-kilobase transcripts in proportion to the level of detectable PDGF-AA protein. Similarly to PDGF-AA, the hepatoma cell-derived GSM has a potent angiogenic activity. Taken together, our results demonstrate that the predominant glucocorticoid suppressible mitogen secreted from rat hepatoma cells is a PDGF A-chain homodimer and suggest that in vivo glucocorticoids may potentially regulate hepatoma growth by modulating PDGF-stimulated tumor vascularization.
 ...
PMID:Identification of the glucocorticoid suppressible mitogen from rat hepatoma cells as an angiogenic platelet-derived growth factor A-chain homodimer. 191 57

Polypeptide growth factors are a class of potent natural biologic mediators which regulate many of the activities of wound healing including cell proliferation, migration, and metabolism. Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) have been shown to regulate DNA and protein synthesis in bone cells in vitro and to interact synergistically to enhance soft tissue wound healing in vivo. We have hypothesized that the combination of PDGF and IGF-I may, therefore, enhance regeneration of both the soft and hard tissue components of the periodontium. To test this hypothesis we performed conventional periodontal surgery on all 4 quadrants of the mouth of 13 beagle dogs with naturally occurring periodontal disease. Following flap reflection, degranulation, and root planing, all premolar teeth in 2 quadrants of each dog received a combination of 3 micrograms of recombinant PDGF-B and IGF-I in a methylcellulose gel, while the premolar teeth in the contralateral quadrants received the gel alone. Teeth in 4 additional animals also received 125I-PDGF or 125I-IGF-I in the treated sites. The clearance rate of the 125I-labeled protein, changes in local bone metabolism, and amount of new bone and cementum with inserting collagen fibers were measured. The clearance studies revealed that the half-life of the factors at the site of application was 3.0 hours for IGF-I and to 4.2 hours for PDGF-B. Greater than 96% of the radio-labeled proteins was cleared by 96 hours and no radioactivity was detected 2 weeks after application. There was a significant (P less than 0.01) 2-fold increase in uptake of the bone-seeking radiopharmaceutical Technetium 99-MDP at 2 and 4 weeks in growth factor treated sites compared to controls, indicating that there was increased metabolic activity within the bone at these sites. Computer-aided histologic analyses of biopsies obtained at 2 and 5 weeks post-operatively revealed a significant (P less than 0.01), 5 to 10 fold increase in new bone and cementum in PDGF-B/IGF-I treated sites at both time points compared to controls receiving the placebo gel. The height and total area of new bone continued to increase from 2 to 5 weeks. The new bone underwent a normal maturation process as judged by histologic appearance. A physiologic periodontal ligament space was also formed between the new bone and new cementum. There was no increase in ankylosis in the treated sites.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. 192 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>