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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 NCBI Skip to main content Skip to navigation Resources How To About NCBI Accesskeys Sign in to NCBI PubMed US National Library of Medicine National Institutes of Health Search termSearch database 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 Genes & Expression Genetics & Medicine Genomes & Maps Homology Literature Proteins Sequence Analysis Taxonomy Training & Tutorials Variation POPULAR PubMed Nucleotide BLAST PubMed Central Gene 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 About NCBI Research at NCBI NCBI Newsletter NCBI FTP Site NCBI on Facebook NCBI on Twitter NCBI on YouTube NLM NIH DHHS USA.gov Copyright | Disclaimer | Privacy | Accessibility | Contact National Center for Biotechnology Information, U.S. National Library of Medicine 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 NCBI Skip to main content Skip to navigation Resources How To About NCBI Accesskeys Sign in to NCBI PubMed US National Library of Medicine National Institutes of Health Search termSearch database 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 Genes & Expression Genetics & Medicine Genomes & Maps Homology Literature Proteins Sequence Analysis Taxonomy Training & Tutorials Variation POPULAR PubMed Nucleotide BLAST PubMed Central Gene 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 About NCBI Research at NCBI NCBI Newsletter NCBI FTP Site NCBI on Facebook NCBI on Twitter NCBI on YouTube NLM NIH DHHS USA.gov Copyright | Disclaimer | Privacy | Accessibility | Contact National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA
