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| - | The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlDisplay Settings:AbstractThe following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlSend to:
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| - | J Cell Biol. 1990 Nov;111(5 Pt 1):2129-38.
| + | |
| - | Possible dissociation of the heparin-binding and mitogenic activities of heparin-binding (acidic fibroblast) growth factor-1 from its receptor-binding activities by site-directed mutagenesis of a single lysine residue.
| + | |
| - | Burgess WH, Shaheen AM, Ravera M, Jaye M, Donohue PJ, Winkles JA.
| + | |
| - | Source
| + | |
| - | Laboratory of Molecular Biology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855.
| + | |
| - | Abstract
| + | |
| - | The fibroblast or heparin-binding growth factors (HBGFs) are thought to be modulators of cell growth and migration, angiogenesis, wound repair, neurite extension, and mesoderm induction. A better understanding of the structural basis for the different activities of these proteins should facilitate the development of agonists and antagonists of specific HBGF activities and identification of the signal transduction pathways involved in the mechanisms of action of these growth factors. Chemical modification studies of Harper and Lobb (Harper, J. W., and R. R. Lobb. 1988. Biochemistry. 27:671-678) implicated lysine 132 in HBGF-1 (acidic fibroblast growth factor) as being important to the heparin-binding, receptor-binding, and mitogenic activities of the protein. We changed lysine 132 to a glutamic acid residue by site-directed mutagenesis of the human cDNA and expressed the mutant protein in Escherichia coli to obtain sufficient quantities for functional studies. Replacement of this lysine with glutamic acid reduces the apparent affinity of HBGF-1 for immobilized heparin (elutes at 0.45 M NaCl vs. 1.1 M NaCl for wild-type). Mitogenic assays established two points: (a) human recombinant HBGF-1 is highly dependent on the presence of heparin for optimal mitogenic activity, and (b) the change of lysine 132 to glutamic acid drastically reduces the specific mitogenic activity of HBGF-1. The poor mitogenic activity of the mutant protein does not appear to be due to a reduced affinity for the HBGF receptor. Similarly, the mutant HBGF-1 can stimulate tyrosine kinase activity and induce protooncogene expression. Differences in the biological properties of the wild-type and mutant proteins were observed in transfection studies. Mutant HBGF-1 expression in transfected NIH 3T3 cells did not induce the same transformed phenotype characteristic of cells expressing wild-type HBGF-1. Together these data indicate that different functional properties of HBGF-1 may be dissociated at the structural level.
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| - | PMID: 1699952 [PubMed - indexed for MEDLINE] PMCID: PMC2116333 Free PMC Article
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| - | The following toggler user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control
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| - | Publication Types, MeSH Terms, Substances, Grant Support
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| - | Research Support, Non-U.S. Gov't
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| - | Research Support, U.S. Gov't, P.H.S.
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| - | MeSH Terms
| + | |
| - | Animals
| + | |
| - | Cells, Cultured
| + | |
| - | Enzyme Activation
| + | |
| - | Fibroblast Growth Factor 1/chemistry*
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| - | Fibroblast Growth Factor 1/physiology
| + | |
| - | Gene Expression Regulation
| + | |
| - | Glutamates
| + | |
| - | Glutamic Acid
| + | |
| - | Heparin/metabolism*
| + | |
| - | Lysine
| + | |
| - | Mitosis/physiology*
| + | |
| - | Mutagenesis, Site-Directed
| + | |
| - | Protein-Tyrosine Kinases/metabolism
| + | |
| - | Proto-Oncogene Proteins/genetics
| + | |
| - | RNA, Messenger/analysis
| + | |
| - | Receptors, Cell Surface/metabolism*
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| - | Receptors, Fibroblast Growth Factor
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| - | Transfection
| + | |
| - | Substances
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| - | Glutamates
| + | |
| - | Proto-Oncogene Proteins
| + | |
| - | RNA, Messenger
| + | |
| - | Receptors, Cell Surface
| + | |
| - | Receptors, Fibroblast Growth Factor
| + | |
| - | Fibroblast Growth Factor 1
| + | |
| - | Glutamic Acid
| + | |
| - | Lysine
| + | |
| - | Heparin
| + | |
| - | Protein-Tyrosine Kinases
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| - | Grant Support
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| - | HL 35762/HL/NHLBI NIH HHS/United States
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| - | HL 39727/HL/NHLBI NIH HHS/United States
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| - | The following toggler user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control
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| - | LinkOut - more resources
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| - | Supplemental Content
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| - | Save items
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| - | The following setswitch user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlAdd to Favorites
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| - | View more options
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| - | Related citations in PubMed
| + | |
| - | Structure-function studies of heparin-binding (acidic fibroblast) growth factor-1 using site-directed mutagenesis.
| + | |
| - | [J Cell Biochem. 1991]
| + | |
| - | Review Structure-function studies of FGF-1: dissociation and partial reconstitution of certain of its biological activities.
| + | |
| - | [Mol Reprod Dev. 1994]
| + | |
| - | Transformed phenotype conferred to NIH/3T3 cells by ectopic expression of heparin-binding growth factor 1/acidic fibroblast growth factor.
| + | |
| - | [In Vitro Cell Dev Biol. 1991]
| + | |
| - | Receptor phenotype underlies differential response of hepatocytes and nonparenchymal cells to heparin-binding fibroblast growth factor type 1 (aFGF) and type 2 (bFGF).
| + | |
| - | [In Vitro Cell Dev Biol. 1992]
| + | |
| - | Review Fibroblast (heparin-binding) growing factors in neuronal development and repair.
| + | |
| - | [Mol Neurobiol. 1988]
| + | |
| - | See reviews...
| + | |
| - | See all...
| + | |
| - | Cited by 18 PubMed Central articles
| + | |
| - | Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors.
| + | |
| - | [J Biol Chem. 2010]
| + | |
| - | Increased protein stability of FGF1 can compensate for its reduced affinity for heparin.
| + | |
| - | [J Biol Chem. 2009]
| + | |
| - | Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity.
| + | |
| - | [EMBO J. 2002]
| + | |
| - | See all...
| + | |
| - | Related information
| + | |
| - | Related Citations
| + | |
| - | Compound (MeSH Keyword)
| + | |
| - | References for this PMC Article
| + | |
| - | Substance (MeSH Keyword)
| + | |
| - | Free in PMC
| + | |
| - | Cited in PMC
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| - | Recent activity
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| - | Clear Turn Off
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| - | Possible dissociation of the heparin-binding and mitogenic activities of heparin...
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| - | PubMed
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| - | See more...
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| - | You are here: NCBI > Literature > PubMedWrite to the Help Desk
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| - | Homology
| + | |
| - | Literature
| + | |
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| - | Sequence Analysis
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| - | 8600 Rockville Pike, Bethesda MD, 20894 USA The following menu user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control
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| - | PubMed
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| - | US National Library of Medicine National Institutes of Health
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| - | Search termSearch database
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| - | The following autocomplete user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlSearch
| + | |
| - | AdvancedHelp
| + | |
| - | Result Filters
| + | |
| - | The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlDisplay Settings:AbstractThe following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlSend to:
| + | |
| - | J Cell Biol. 1990 Nov;111(5 Pt 1):2129-38.
| + | |
| - | Possible dissociation of the heparin-binding and mitogenic activities of heparin-binding (acidic fibroblast) growth factor-1 from its receptor-binding activities by site-directed mutagenesis of a single lysine residue.
| + | |
| - | Burgess WH, Shaheen AM, Ravera M, Jaye M, Donohue PJ, Winkles JA.
| + | |
| - | Source
| + | |
| - | Laboratory of Molecular Biology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855.
| + | |
| - | Abstract
| + | |
| - | The fibroblast or heparin-binding growth factors (HBGFs) are thought to be modulators of cell growth and migration, angiogenesis, wound repair, neurite extension, and mesoderm induction. A better understanding of the structural basis for the different activities of these proteins should facilitate the development of agonists and antagonists of specific HBGF activities and identification of the signal transduction pathways involved in the mechanisms of action of these growth factors. Chemical modification studies of Harper and Lobb (Harper, J. W., and R. R. Lobb. 1988. Biochemistry. 27:671-678) implicated lysine 132 in HBGF-1 (acidic fibroblast growth factor) as being important to the heparin-binding, receptor-binding, and mitogenic activities of the protein. We changed lysine 132 to a glutamic acid residue by site-directed mutagenesis of the human cDNA and expressed the mutant protein in Escherichia coli to obtain sufficient quantities for functional studies. Replacement of this lysine with glutamic acid reduces the apparent affinity of HBGF-1 for immobilized heparin (elutes at 0.45 M NaCl vs. 1.1 M NaCl for wild-type). Mitogenic assays established two points: (a) human recombinant HBGF-1 is highly dependent on the presence of heparin for optimal mitogenic activity, and (b) the change of lysine 132 to glutamic acid drastically reduces the specific mitogenic activity of HBGF-1. The poor mitogenic activity of the mutant protein does not appear to be due to a reduced affinity for the HBGF receptor. Similarly, the mutant HBGF-1 can stimulate tyrosine kinase activity and induce protooncogene expression. Differences in the biological properties of the wild-type and mutant proteins were observed in transfection studies. Mutant HBGF-1 expression in transfected NIH 3T3 cells did not induce the same transformed phenotype characteristic of cells expressing wild-type HBGF-1. Together these data indicate that different functional properties of HBGF-1 may be dissociated at the structural level.
| + | |
| - | PMID: 1699952 [PubMed - indexed for MEDLINE] PMCID: PMC2116333 Free PMC Article
| + | |
| - | The following toggler user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control
| + | |
| - | Publication Types, MeSH Terms, Substances, Grant Support
| + | |
| - | Publication Types
| + | |
| - | Research Support, Non-U.S. Gov't
| + | |
| - | Research Support, U.S. Gov't, P.H.S.
| + | |
| - | MeSH Terms
| + | |
| - | Animals
| + | |
| - | Cells, Cultured
| + | |
| - | Enzyme Activation
| + | |
| - | Fibroblast Growth Factor 1/chemistry*
| + | |
| - | Fibroblast Growth Factor 1/physiology
| + | |
| - | Gene Expression Regulation
| + | |
| - | Glutamates
| + | |
| - | Glutamic Acid
| + | |
| - | Heparin/metabolism*
| + | |
| - | Lysine
| + | |
| - | Mitosis/physiology*
| + | |
| - | Mutagenesis, Site-Directed
| + | |
| - | Protein-Tyrosine Kinases/metabolism
| + | |
| - | Proto-Oncogene Proteins/genetics
| + | |
| - | RNA, Messenger/analysis
| + | |
| - | Receptors, Cell Surface/metabolism*
| + | |
| - | Receptors, Fibroblast Growth Factor
| + | |
| - | Transfection
| + | |
| - | Substances
| + | |
| - | Glutamates
| + | |
| - | Proto-Oncogene Proteins
| + | |
| - | RNA, Messenger
| + | |
| - | Receptors, Cell Surface
| + | |
| - | Receptors, Fibroblast Growth Factor
| + | |
| - | Fibroblast Growth Factor 1
| + | |
| - | Glutamic Acid
| + | |
| - | Lysine
| + | |
| - | Heparin
| + | |
| - | Protein-Tyrosine Kinases
| + | |
| - | Grant Support
| + | |
| - | HL 35762/HL/NHLBI NIH HHS/United States
| + | |
| - | HL 39727/HL/NHLBI NIH HHS/United States
| + | |
| - | The following toggler user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface control
| + | |
| - | LinkOut - more resources
| + | |
| - | Supplemental Content
| + | |
| - |
| + | |
| - | Save items
| + | |
| - | The following setswitch user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlAdd to Favorites
| + | |
| - | View more options
| + | |
| - | Related citations in PubMed
| + | |
| - | Structure-function studies of heparin-binding (acidic fibroblast) growth factor-1 using site-directed mutagenesis.
| + | |
| - | [J Cell Biochem. 1991]
| + | |
| - | Review Structure-function studies of FGF-1: dissociation and partial reconstitution of certain of its biological activities.
| + | |
| - | [Mol Reprod Dev. 1994]
| + | |
| - | Transformed phenotype conferred to NIH/3T3 cells by ectopic expression of heparin-binding growth factor 1/acidic fibroblast growth factor.
| + | |
| - | [In Vitro Cell Dev Biol. 1991]
| + | |
| - | Receptor phenotype underlies differential response of hepatocytes and nonparenchymal cells to heparin-binding fibroblast growth factor type 1 (aFGF) and type 2 (bFGF).
| + | |
| - | [In Vitro Cell Dev Biol. 1992]
| + | |
| - | Review Fibroblast (heparin-binding) growing factors in neuronal development and repair.
| + | |
| - | [Mol Neurobiol. 1988]
| + | |
| - | See reviews...
| + | |
| - | See all...
| + | |
| - | Cited by 18 PubMed Central articles
| + | |
| - | Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors.
| + | |
| - | [J Biol Chem. 2010]
| + | |
| - | Increased protein stability of FGF1 can compensate for its reduced affinity for heparin.
| + | |
| - | [J Biol Chem. 2009]
| + | |
| - | Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity.
| + | |
| - | [EMBO J. 2002]
| + | |
| - | See all...
| + | |
| - | Related information
| + | |
| - | Related Citations
| + | |
| - | Compound (MeSH Keyword)
| + | |
| - | References for this PMC Article
| + | |
| - | Substance (MeSH Keyword)
| + | |
| - | Free in PMC
| + | |
| - | Cited in PMC
| + | |
| - | Recent activity
| + | |
| - | Clear Turn Off
| + | |
| - | Possible dissociation of the heparin-binding and mitogenic activities of heparin...
| + | |
| - | PubMed
| + | |
| - | See more...
| + | |
| - | You are here: NCBI > Literature > PubMedWrite to the Help Desk
| + | |
| - | Simple NCBI Directory
| + | |
| - | GETTING STARTED
| + | |
| - | NCBI Education
| + | |
| - | NCBI Help Manual
| + | |
| - | NCBI Handbook
| + | |
| - | Training & Tutorials
| + | |
| - | RESOURCES
| + | |
| - | Chemicals & Bioassays
| + | |
| - | Data & Software
| + | |
| - | DNA & RNA
| + | |
| - | Domains & Structures
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| - | Genes & Expression
| + | |
| - | Genetics & Medicine
| + | |
| - | Genomes & Maps
| + | |
| - | Homology
| + | |
| - | Literature
| + | |
| - | Proteins
| + | |
| - | Sequence Analysis
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| - | Taxonomy
| + | |
| - | Training & Tutorials
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| - | Variation
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| - | POPULAR
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| - | PubMed
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| - | Nucleotide
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| + | |
| - | PubMed Central
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| - | Gene
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| - | Bookshelf
| + | |
| - | Protein
| + | |
| - | OMIM
| + | |
| - | Genome
| + | |
| - | SNP
| + | |
| - | Structure
| + | |
| - | FEATURED
| + | |
| - | Genetic Testing Registry
| + | |
| - | PubMed Health
| + | |
| - | GenBank
| + | |
| - | Reference Sequences
| + | |
| - | Map Viewer
| + | |
| - | Human Genome
| + | |
| - | Mouse Genome
| + | |
| - | Influenza Virus
| + | |
| - | Primer-BLAST
| + | |
| - | Sequence Read Archive
| + | |
| - | NCBI INFORMATION
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| - | NLM NIH DHHS USA.gov
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| - | National Center for Biotechnology Information, U.S. National Library of Medicine
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| - | 8600 Rockville Pike, Bethesda MD, 20894 USA
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