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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deletion scanning mutagenesis within the transforming region of the v-sis oncogene was used to dissect structure-function relationships. Mutations affecting codons within a domain encoding amino acids 136 through 148 had no effect upon homodimer formation or recognition by antisera which detect determinants dependent upon native intrachain disulfide linkages, yet the same mutations completely abolished transforming activity. A platelet-derived growth factor B (PDGF B) monoclonal antibody that prevents its interaction with PDGF receptors recognized v-sis, delta 142 (deletion of codon 142), and delta 148 but not delta 136, delta 137, or delta 139 mutants. These findings mapped the epitope recognized by this monoclonal antibody to include amino acid residues 136 to 139. Furthermore, mutations in the codon 136 to 148 domain caused markedly impaired ability to induce PDGF receptor tyrosine phosphorylation. Thus, subtle conformational alterations in this small domain critically affect PDGF receptor recognition and/or functional activation.
Mol Cell Biol 1990 Oct
PMID:A small v-sis/platelet-derived growth factor (PDGF) B-protein domain in which subtle conformational changes abrogate PDGF receptor interaction and transforming activity. 169 31

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)
Am J Respir Cell Mol Biol 1991 Oct
PMID:Platelet-derived growth factor and growth-related genes in rat lung. I. Developmental expression. 191 Aug 22

Normal lung structure is maintained by the presence of mesenchymal cells and their extracellular matrix products. The slow normal turnover of these cells is disrupted in fibrotic disorders, resulting in the in situ accumulation of mesenchymal cells and their extracellular matrix leading to a progressive alveolar wall thickening. Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic disorder of the lung characterized by a diffuse interstitial and intra-alveolar inflammation dominated by macrophages and polymorphonuclear neutrophils. Evaluation of alveolar macrophages (AM) obtained by bronchoalveolar lavage has previously shown that AM from normal individuals spontaneously release small amounts of platelet-derived growth factor (PDGF), a chemotactic and growth factor for mesenchymal cells, whereas AM from IPF patients spontaneously release increased amounts of biologically active PDGF, suggesting its involvement in mesenchymal cell accumulation. However, other cells such as endothelial cells and vascular smooth muscle cells can also release PDGF in vitro. In order to specify PDGF location in lung parenchyma, open lung biopsies from normal individuals and IPF patients were examined by immunohistochemistry using an anti-PDGF antibody and by in situ hybridization using PDGF A-chain and B-chain gene probes. In normal as well as in fibrotic lung, PDGF was only present in relation with interstitial macrophages but not with any other inflammatory cells or mesenchymal cells. Furthermore, the percentage of PDGF-positive macrophages in IPF was 3-fold increased in comparison to normal lung. In addition, the percentage of PDGF-positive macrophages was the same in fibrotic and nonfibrotic areas of IPF lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Dec
PMID:Presence of platelet-derived growth factor in normal and fibrotic lung is specifically associated with interstitial macrophages, while both interstitial macrophages and alveolar epithelial cells express the c-sis proto-oncogene. 195 75

We have examined the expression of mRNAs for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), EGF receptor (EGFR), PDGF-A chain (PDGFA), PDGF-B chain (PDGFB) and PDGF receptor (PDGFR) genes in seven human colorectal carcinoma cell lines and 18 human colorectal carcinomas. In surgically resected specimens of the 18 colorectal tumors, TGF-alpha, EGFR, PDGFA, PDGFB and PDGFR mRNAs were detected at various levels in 15 (83%), 9 (50%), 18 (100%), 8 (44%) and 12 (67%), respectively. They were also detected in normal tissues. Interestingly, EGF mRNA was detected in only five (28%) of the tumors, but not in normal mucosa. Expression of EGF was also confirmed immunohistochemically in tumor cells. Of the five tumors expressing EGF, four expressed EGFR mRNA and showed a tendency to invade veins and lymphatics. All the colorectal carcinoma cell lines expressed TGF-alpha mRNA, and five cell lines expressed EGFR mRNA simultaneously. Production of TGF-alpha protein by DLD-1 and CoLo320DM cells was confirmed by TGF-alpha specific monoclonal antibody binding assay. The spontaneous 3H-thymidine uptake by DLD-1 was suppressed by an anti-TGF-alpha monoclonal antibody. PDGFA and PDGFB mRNA were also expressed in four cell lines, but PDGFR and EGF mRNA was not detected. These results suggest that human colorectal carcinomas express multi-loops of growth factors and that TGF-alpha produced by tumor cells functions as an autocrine growth factor in human colonic carcinoma.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Expression of several growth factors and their receptor genes in human colon carcinomas. 198 Jul 64

We have cloned and characterized a new member of the receptor tyrosine kinase family. The cDNA clone, isolated from a rat olfactory cDNA library, has considerable homology to the family of receptors that includes the colony-stimulating factor 1 receptor, the c-kit proto-oncogene, and the platelet-derived growth factor (PDGF) receptors. Analysis of DNA sequence homology, ligand-binding, and ligand-stimulated phosphorylation data suggests that this clone encodes the rat PDGF-A/B or alpha-receptor. Comparison of its sequence to those of other receptors allows us to postulate a mechanism for receptor dimerization and activation. The expression of the rat alpha-PDGF receptor in nonneuronal cells of the olfactory epithelium and in the olfactory bulb is consistent with a role for PDGF in glial cell generation.
Mol Cell Biol 1990 May
PMID:Isolation and characterization of the alpha platelet-derived growth factor receptor from rat olfactory epithelium. 215 69

Retinoic acid together with dibutyryl cyclic AMP stimulated transcription of the platelet-derived growth factor alpha-receptor gene in embryonal carcinoma cells (line F9). Processed mRNA transcripts appeared within 4 h after exposure to these agents, and functional alpha:alpha homodimers appeared within 24 h.
Mol Cell Biol 1990 Dec
PMID:Retinoic acid promotes transcription of the platelet-derived growth factor alpha-receptor gene. 217 16

Platelet-derived growth factor (PDGF) is a potent mitogen in human serum which specifically stimulates the proliferation of mesenchymal cells. We have now examined normal human mammary epithelial cells (HMEC) derived from reduction mammaplasties and grown in a serum-free defined medium. Medium conditioned by HMEC contained a PDGF-like activity that competed with [125I]PDGF for binding to PDGF receptors in normal human fibroblasts. When conditioned media were incubated with antiserum specific for either PDGF-A or PDGF-B, only PDGF-A antiserum was capable of inhibiting binding of conditioned media to PDGF receptors. Using an RNase protection assay, mRNA from normal HMEC was probed for both the PDGF-A and PDGF-B chains. Little or no PDGF-B was found in HMEC strains, while a strong signal was seen with the PDGF-A probe. When HMEC were grown in the presence of transforming growth factor-beta (TGF beta) for 48 h, inhibition of growth was observed in association with a 20- to 40-fold stimulation of PDGF-B mRNA and a 2-fold stimulation of PDGF-A mRNA. This mRNA induction was extremely rapid (within 1 h), and secreted PDGF activity was induced 2- to 3-fold. Two other HMEC growth inhibitors and differentiating agents, sodium butyrate and phorbol ester 12-O-tetradecanoylphorbol-13-acetate, had no effect on PDGF mRNA regulation. The current study suggests that PDGF gene induction is an extremely rapid and specific indicator of TGF beta function regardless of whether TGF beta is acting in a growth stimulatory or inhibitory manner. Any role of PDGF-B in TGF beta modulation of differentiation of normal or malignant mammary gland remains to be determined.
Mol Endocrinol 1990 Jul
PMID:Transforming growth factor-beta induces platelet-derived growth factor (PDGF) messenger RNA and PDGF secretion while inhibiting growth in normal human mammary epithelial cells. 217 25

We have studied mRNA levels for a variety of growth factors in biopsy specimens from malignant, benign and normal breast tissue. We found TGFb mRNA in all breast cancers and neoplastic breast tissues but the level of the TGFb mRNA were found to be higher in breast cancer (P = 0.01). TGFa mRNA was detected in a similar proportion of cancers as in neoplastic breast tissues but the TGFa receptor EGFR mRNA was detected in only 55% of breast cancers but in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inverted related to oestrogen receptor status and coexpression of TGFa and EGFR was observed in 28% of carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). PDGF a and b chain transcripts coexisted in all normal and malignant breast tissue. Insulin-like growth factor II mRNA was present in all 15 samples of non-malignant breast tissue but in only 11 of 21 (52%) of carcinomas.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Growth factor expression in breast tissue. 228 95

Expression vectors encoding cDNAs for the human platelet-derived growth factor (PDGF) A-chain (pJKl) and murine dihydrofolate reductase (pTKDHFR) were cotransfected into dihydrofolate reductase-deficient Chinese hamster ovary cells. Methotrexate-induced coamplification of clones, expressing PDGF A-chain resulted in enhanced levels of A-chain-specific DNA, RNA and protein. A 30,500 Mr protein was immunoprecipitated with PDGF antisera from the conditioned media of metabolically labeled cells. Reducing conditions resolved the A-chain-specific protein into two polypeptides of 16,500 and 17,000 Mr, confirming the homodimeric nature of the recombinant A-chain protein. The recombinant PDGF A-chain produced constitutively by these amplified clones proved to be mitogenically active. The secretion of a recombinant PDGF A-chain into conditioned media may provide a continuous and abundant source of PDGF A.A dimers, normally produced by specific tissues in only minute quantities. Future purification of the recombinant homodimeric A-chain will allow the assessment of its ability to function in clinical applications such as wound healing.
Mol Biol Med 1989 Jun
PMID:Expression of mitogenically active human recombinant platelet-derived growth factor A-chain. 248 5

Phorbol esters bind to and activate a family of Protein Kinase C (PKC) proteins, although the degree to which the various PKC forms mediate specific biological functions is unknown. We and others have previously shown that, after exposure to phorbol esters, cultured fibroblasts exhibit increased expression of the mRNA encoding the HepG2/brain glucose transporter (GT mRNA). We therefore studied phorbol ester regulation of GT mRNA in rat fibroblasts which do (R6-PKC3) or do not (R6-C1) stably overproduce a full-length cDNA encoding the PKC beta 1 isotype. When PKC beta 1 is overproduced in a cell that normally has undetectable levels, it is capable of increasing HepG2/brain GT mRNA in response to alpha-D-glucose phorbol 12-myristate 13-acetate (TPA). The level of GT mRNA is maximally induced 6 to 8-fold over basal levels 6 h after exposure to TPA (10 ng/ml) in R6-PKC3 cells that overproduce PKC beta 1, but only 2-fold over basal levels in the control R6-C1 cells. This TPA induced increase in the level of GT mRNA was observed as early as 1 h, peaked by 6-8 h and decreased markedly by 24 h in both cell types. The effect of PKC beta 1 on GT mRNA expression is probably mediated through enhancement of transcription, since the stability of GT mRNA was only minimally affected by TPA. Unlike the enhancement of TPA induced GT mRNA expression caused by overexpression of PKC beta 1, the responses of GT mRNA to calf serum, platelet-derived growth factor, epidermal growth factor, insulin or insulin-like growth factor-1 were the same in both cell types. After pretreatment with 1000 ng/ml TPA in 0.5% calf serum for 24 h, PKC activity was down-regulated and both R6-C1 and R6-PKC3 cells showed complete down-regulation of the GT mRNA responses to an additional treatment with 1000 ng/ml TPA. In contrast to the marked loss of responsiveness to TPA and PKC down-regulation, the responses of GT mRNA to serum, PDGF, EGF, insulin and IGF-1 were unaffected by down-regulation. Thus, our results provide direct evidence for both PKC-dependent and independent pathways regulating GT gene expression. Furthermore, it appears that the level of PKC beta 1 production, rather than down-stream signal transduction events, is the rate-limiting step in the pathway by which TPA induces an increase in GT mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Endocrinol 1989 Dec
PMID:Overproduction of the beta 1 form of protein kinase C enhances phorbol ester induction of glucose transporter mRNA. 262 36


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