| Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant. | |
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MedLine Citation:
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PMID: 8321214 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A non-receptor-binding mutant of the platelet-derived growth factor (PDGF) A chain, PDGF-0, was generated by exchanging 7 amino acids in the sequence. The mutant chains formed dimers that were similar to wild-type PDGF-AA with regard to stability and rate of processing to the mature 30-kDa secreted forms. Moreover, the mutant chains formed disulfide-bonded heterodimers with the PDGF B chain in NIH 3T3 cells heterodimer underwent the same processing and secretion as PDGF-AB. Transfection of c-sis-expressing 3T3 cells with PDGF-0 significantly inhibited the transformed phenotype of these cells, as determined by the following criteria. (i) Compared with PDGF-0-negative clones, PDGF-0-producing clones showed a reverted morphology. (ii) Clones producing PDGF-0 grew more slowly than PDGF-0-negative clones, with a fivefold difference in cell number after 14 days in culture. (iii) The expression of PDGF-0 completely inhibited the ability of the c-sis-expressing 3T3 cells to form colonies in soft agar; this inhibition was overcome by the addition of recombinant PDGF-BB to the culture medium, showing that the lack of colony formation of these cells was not due to a general unresponsiveness to PDGF. The specific expression of a PDGF-0/PDGF wild-type heterodimer in COS cells revealed that the affinity of the mutant heterodimer for the PDGF alpha receptor was decreased by approximately 50-fold compared with that of PDGF-AA. Thus, we show that a non-receptor-binding PDGF A-chain mutant neutralizes in a trans-dominant manner the autocrine transforming potential of the c-sis/PDGF B chain by forming low-affinity heterodimers with wild-type PDGF chains. This method of specifically antagonizing the effect of PDGF may be useful in investigations of the role of PDGF in normal and pathological conditions. |
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Authors:
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F S Vassbotn; M Andersson; B Westermark; C H Heldin; A Ostman |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Molecular and cellular biology Volume: 13 ISSN: 0270-7306 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 1993 Jul |
Date Detail:
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Created Date: 1993-07-30 Completed Date: 1993-07-30 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4066-76 Citation Subset: IM |
Affiliation:
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Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Animals Cell Line Cell Transformation, Neoplastic / genetics* Cells, Cultured Chromatography, High Pressure Liquid Cloning, Molecular Humans Kinetics Mice Mutation Phenotype Platelet-Derived Growth Factor / genetics*, metabolism Precipitin Tests Receptors, Platelet-Derived Growth Factor / metabolism Transfection Tumor Cells, Cultured Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Platelet-Derived Growth Factor; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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