Interaction of Endothelial Cell Growth Factor with Heparin: Characterization by Receptor and Antibody Recognition

Endothelial cell growth factor (ECGF) binds specifically in vitro to membrane receptors present on the surface of several cell types, including murine and human endothelial cells and fibroblasts. Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor pre...

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Veröffentlicht in:Proc. Natl. Acad. Sci. U.S.A.; (United States) 1985-09, Vol.82 (18), p.6138-6142
Hauptverfasser: Schreiber, Alain B., Kenney, John, Kowalski, William J., Friesel, Robert, Mehlman, Tevie, Maciag, Thomas
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container_issue 18
container_start_page 6138
container_title Proc. Natl. Acad. Sci. U.S.A.; (United States)
container_volume 82
creator Schreiber, Alain B.
Kenney, John
Kowalski, William J.
Friesel, Robert
Mehlman, Tevie
Maciag, Thomas
description Endothelial cell growth factor (ECGF) binds specifically in vitro to membrane receptors present on the surface of several cell types, including murine and human endothelial cells and fibroblasts. Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor prevent receptor occupancy by the ligand. Heparin interacts structurally with ECGF [Maciag, T., Mehlman, T., Friesel, R. & Schreiber, A. B. (1984) Science 225, 932-935], potentiates the mitogenic activity of the polypeptide, restores the biological activity to inactivate ECGF, enhances the affinity of the ligand to cell surface receptors, and modifies antibody recognition of ECGF. These data suggest that the association between heparin and ECGF induces a conformational change in the polypeptide that increases or stabilizes the biological activity of the mitogen.
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Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor prevent receptor occupancy by the ligand. Heparin interacts structurally with ECGF [Maciag, T., Mehlman, T., Friesel, R. &amp; Schreiber, A. B. (1984) Science 225, 932-935], potentiates the mitogenic activity of the polypeptide, restores the biological activity to inactivate ECGF, enhances the affinity of the ligand to cell surface receptors, and modifies antibody recognition of ECGF. These data suggest that the association between heparin and ECGF induces a conformational change in the polypeptide that increases or stabilizes the biological activity of the mitogen.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.82.18.6138</identifier><identifier>PMID: 2412230</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>550601 - Medicine- Unsealed Radionuclides in Diagnostics ; AMINES ; ANIMAL CELLS ; ANIMAL TISSUES ; ANIMALS ; ANTIBODIES ; ANTICOAGULANTS ; BETA DECAY RADIOISOTOPES ; Biological and medical sciences ; BODY ; CARBOHYDRATES ; CELL CONSTITUENTS ; Cell Division - drug effects ; Cell growth ; CELL MEMBRANES ; Cell physiology ; Cells ; Cells, Cultured ; CONFIGURATION INTERACTION ; CONFORMATIONAL CHANGES ; CONNECTIVE TISSUE CELLS ; DAYS LIVING RADIOISOTOPES ; DRUGS ; ELECTRON CAPTURE RADIOISOTOPES ; Endothelial cells ; Endothelial Growth Factors ; ENDOTHELIUM ; Endothelium - metabolism ; Epitopes ; FIBROBLASTS ; Fibroblasts - metabolism ; Fundamental and applied biological sciences. Psychology ; Growth Substances - immunology ; Growth Substances - metabolism ; HEMATOLOGIC AGENTS ; HEPARIN ; Heparin - pharmacology ; Human umbilical vein endothelial cells ; Humans ; INTERMEDIATE MASS NUCLEI ; IODINE 125 ; IODINE ISOTOPES ; ISOTOPE APPLICATIONS ; ISOTOPES ; MAMMALS ; MAN ; MEMBRANES ; MICE ; Mitosis ; Molecular and cellular biology ; MONOCLONAL ANTIBODIES ; MUCOPOLYSACCHARIDES ; NUCLEI ; ODD-EVEN NUCLEI ; ORGANIC COMPOUNDS ; ORGANIC SULFUR COMPOUNDS ; PEPTIDES ; POLYPEPTIDES ; POLYSACCHARIDES ; PRIMATES ; Protein Binding - drug effects ; Protein Conformation - drug effects ; PROTEINS ; RADIOISOTOPES ; RADIOLOGY AND NUCLEAR MEDICINE ; RADIONUCLIDE KINETICS ; RADIORECEPTOR ASSAY ; Receptors ; Receptors, Mitogen - metabolism ; Receptors, Vascular Endothelial Growth Factor ; Responses to growth factors, tumor promotors, other factors ; RODENTS ; SACCHARIDES ; SOMATIC CELLS ; TISSUES ; TRACER TECHNIQUES ; Ungulates ; VERTEBRATES</subject><ispartof>Proc. Natl. Acad. Sci. 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Natl. Acad. Sci. U.S.A.; (United States)</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Endothelial cell growth factor (ECGF) binds specifically in vitro to membrane receptors present on the surface of several cell types, including murine and human endothelial cells and fibroblasts. Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor prevent receptor occupancy by the ligand. Heparin interacts structurally with ECGF [Maciag, T., Mehlman, T., Friesel, R. &amp; Schreiber, A. B. (1984) Science 225, 932-935], potentiates the mitogenic activity of the polypeptide, restores the biological activity to inactivate ECGF, enhances the affinity of the ligand to cell surface receptors, and modifies antibody recognition of ECGF. These data suggest that the association between heparin and ECGF induces a conformational change in the polypeptide that increases or stabilizes the biological activity of the mitogen.</description><subject>550601 - Medicine- Unsealed Radionuclides in Diagnostics</subject><subject>AMINES</subject><subject>ANIMAL CELLS</subject><subject>ANIMAL TISSUES</subject><subject>ANIMALS</subject><subject>ANTIBODIES</subject><subject>ANTICOAGULANTS</subject><subject>BETA DECAY RADIOISOTOPES</subject><subject>Biological and medical sciences</subject><subject>BODY</subject><subject>CARBOHYDRATES</subject><subject>CELL CONSTITUENTS</subject><subject>Cell Division - drug effects</subject><subject>Cell growth</subject><subject>CELL MEMBRANES</subject><subject>Cell physiology</subject><subject>Cells</subject><subject>Cells, Cultured</subject><subject>CONFIGURATION INTERACTION</subject><subject>CONFORMATIONAL CHANGES</subject><subject>CONNECTIVE TISSUE CELLS</subject><subject>DAYS LIVING RADIOISOTOPES</subject><subject>DRUGS</subject><subject>ELECTRON CAPTURE RADIOISOTOPES</subject><subject>Endothelial cells</subject><subject>Endothelial Growth Factors</subject><subject>ENDOTHELIUM</subject><subject>Endothelium - metabolism</subject><subject>Epitopes</subject><subject>FIBROBLASTS</subject><subject>Fibroblasts - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Growth Substances - immunology</subject><subject>Growth Substances - metabolism</subject><subject>HEMATOLOGIC AGENTS</subject><subject>HEPARIN</subject><subject>Heparin - pharmacology</subject><subject>Human umbilical vein endothelial cells</subject><subject>Humans</subject><subject>INTERMEDIATE MASS NUCLEI</subject><subject>IODINE 125</subject><subject>IODINE ISOTOPES</subject><subject>ISOTOPE APPLICATIONS</subject><subject>ISOTOPES</subject><subject>MAMMALS</subject><subject>MAN</subject><subject>MEMBRANES</subject><subject>MICE</subject><subject>Mitosis</subject><subject>Molecular and cellular biology</subject><subject>MONOCLONAL ANTIBODIES</subject><subject>MUCOPOLYSACCHARIDES</subject><subject>NUCLEI</subject><subject>ODD-EVEN NUCLEI</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC SULFUR COMPOUNDS</subject><subject>PEPTIDES</subject><subject>POLYPEPTIDES</subject><subject>POLYSACCHARIDES</subject><subject>PRIMATES</subject><subject>Protein Binding - drug effects</subject><subject>Protein Conformation - drug effects</subject><subject>PROTEINS</subject><subject>RADIOISOTOPES</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>RADIONUCLIDE KINETICS</subject><subject>RADIORECEPTOR ASSAY</subject><subject>Receptors</subject><subject>Receptors, Mitogen - metabolism</subject><subject>Receptors, Vascular Endothelial Growth Factor</subject><subject>Responses to growth factors, tumor promotors, other factors</subject><subject>RODENTS</subject><subject>SACCHARIDES</subject><subject>SOMATIC CELLS</subject><subject>TISSUES</subject><subject>TRACER TECHNIQUES</subject><subject>Ungulates</subject><subject>VERTEBRATES</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kd1rFDEUxYModV19FgRlENGn2eZzkgg-lKVfUBBEn0Mmk-mkzCbbJGutf72Z7rDWF59yyfndew_3APAawRWCnBxvvU4rgVdIrBpExBOwQFCiuqESPgULCDGvBcX0OXiR0g2EUDIBj8ARpghjAhfg9tJnG7XJLvgq9NWp70Ie7Oj0WK3tOFbnMdzloTorSIjVnSv1hd3q6Pznaj3oqdVG91s_DGjvq2_W2O2Eat9VJz67NnQPv-Hauwl6CZ71ekz21fwuwY-z0-_ri_rq6_nl-uSqNgzxXHPNKWcCUd5oLRHjHaYS6UbyrmdYMmtI12LSC9tj3bUGmpZL2qK-aUXHO0iW4Mt-7nbXbmxnrM9Rj2ob3UbHexW0U_8q3g3qOvxURCJYTrsE7_f9IWWnknHZmsEE763JqiEQUioK9HFeEsPtzqasNi6ZcjftbdglxRvCKMWkgMd70MSQUrT9wQiCakpSTUkqgRUSakqydLx97P_Az9EV_cOs62T02EftjUsHTFBJOEIFezdj0_yD-njPp_8Cqt-NY7a_ciHf7MmbVAL-a4hJxsgfqDbJ7A</recordid><startdate>19850901</startdate><enddate>19850901</enddate><creator>Schreiber, Alain B.</creator><creator>Kenney, John</creator><creator>Kowalski, William J.</creator><creator>Friesel, Robert</creator><creator>Mehlman, Tevie</creator><creator>Maciag, Thomas</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>19850901</creationdate><title>Interaction of Endothelial Cell Growth Factor with Heparin: Characterization by Receptor and Antibody Recognition</title><author>Schreiber, Alain B. ; Kenney, John ; Kowalski, William J. ; Friesel, Robert ; Mehlman, Tevie ; Maciag, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-7a747581476aa9157d2491a697df5295ec3db23f8ef2adbc0cb794b1f6b8d7d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>550601 - Medicine- Unsealed Radionuclides in Diagnostics</topic><topic>AMINES</topic><topic>ANIMAL CELLS</topic><topic>ANIMAL TISSUES</topic><topic>ANIMALS</topic><topic>ANTIBODIES</topic><topic>ANTICOAGULANTS</topic><topic>BETA DECAY RADIOISOTOPES</topic><topic>Biological and medical sciences</topic><topic>BODY</topic><topic>CARBOHYDRATES</topic><topic>CELL CONSTITUENTS</topic><topic>Cell Division - drug effects</topic><topic>Cell growth</topic><topic>CELL MEMBRANES</topic><topic>Cell physiology</topic><topic>Cells</topic><topic>Cells, Cultured</topic><topic>CONFIGURATION INTERACTION</topic><topic>CONFORMATIONAL CHANGES</topic><topic>CONNECTIVE TISSUE CELLS</topic><topic>DAYS LIVING RADIOISOTOPES</topic><topic>DRUGS</topic><topic>ELECTRON CAPTURE RADIOISOTOPES</topic><topic>Endothelial cells</topic><topic>Endothelial Growth Factors</topic><topic>ENDOTHELIUM</topic><topic>Endothelium - metabolism</topic><topic>Epitopes</topic><topic>FIBROBLASTS</topic><topic>Fibroblasts - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Growth Substances - immunology</topic><topic>Growth Substances - metabolism</topic><topic>HEMATOLOGIC AGENTS</topic><topic>HEPARIN</topic><topic>Heparin - pharmacology</topic><topic>Human umbilical vein endothelial cells</topic><topic>Humans</topic><topic>INTERMEDIATE MASS NUCLEI</topic><topic>IODINE 125</topic><topic>IODINE ISOTOPES</topic><topic>ISOTOPE APPLICATIONS</topic><topic>ISOTOPES</topic><topic>MAMMALS</topic><topic>MAN</topic><topic>MEMBRANES</topic><topic>MICE</topic><topic>Mitosis</topic><topic>Molecular and cellular biology</topic><topic>MONOCLONAL ANTIBODIES</topic><topic>MUCOPOLYSACCHARIDES</topic><topic>NUCLEI</topic><topic>ODD-EVEN NUCLEI</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC SULFUR COMPOUNDS</topic><topic>PEPTIDES</topic><topic>POLYPEPTIDES</topic><topic>POLYSACCHARIDES</topic><topic>PRIMATES</topic><topic>Protein Binding - drug effects</topic><topic>Protein Conformation - drug effects</topic><topic>PROTEINS</topic><topic>RADIOISOTOPES</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>RADIONUCLIDE KINETICS</topic><topic>RADIORECEPTOR ASSAY</topic><topic>Receptors</topic><topic>Receptors, Mitogen - metabolism</topic><topic>Receptors, Vascular Endothelial Growth Factor</topic><topic>Responses to growth factors, tumor promotors, other factors</topic><topic>RODENTS</topic><topic>SACCHARIDES</topic><topic>SOMATIC CELLS</topic><topic>TISSUES</topic><topic>TRACER TECHNIQUES</topic><topic>Ungulates</topic><topic>VERTEBRATES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schreiber, Alain B.</creatorcontrib><creatorcontrib>Kenney, John</creatorcontrib><creatorcontrib>Kowalski, William J.</creatorcontrib><creatorcontrib>Friesel, Robert</creatorcontrib><creatorcontrib>Mehlman, Tevie</creatorcontrib><creatorcontrib>Maciag, Thomas</creatorcontrib><creatorcontrib>Institute of Biological Sciences, Palo Alto, CA</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proc. 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U.S.A.; (United States)</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1985-09-01</date><risdate>1985</risdate><volume>82</volume><issue>18</issue><spage>6138</spage><epage>6142</epage><pages>6138-6142</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Endothelial cell growth factor (ECGF) binds specifically in vitro to membrane receptors present on the surface of several cell types, including murine and human endothelial cells and fibroblasts. Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor prevent receptor occupancy by the ligand. Heparin interacts structurally with ECGF [Maciag, T., Mehlman, T., Friesel, R. &amp; Schreiber, A. B. (1984) Science 225, 932-935], potentiates the mitogenic activity of the polypeptide, restores the biological activity to inactivate ECGF, enhances the affinity of the ligand to cell surface receptors, and modifies antibody recognition of ECGF. These data suggest that the association between heparin and ECGF induces a conformational change in the polypeptide that increases or stabilizes the biological activity of the mitogen.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>2412230</pmid><doi>10.1073/pnas.82.18.6138</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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subjects 550601 - Medicine- Unsealed Radionuclides in Diagnostics
AMINES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIBODIES
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
Biological and medical sciences
BODY
CARBOHYDRATES
CELL CONSTITUENTS
Cell Division - drug effects
Cell growth
CELL MEMBRANES
Cell physiology
Cells
Cells, Cultured
CONFIGURATION INTERACTION
CONFORMATIONAL CHANGES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
Endothelial cells
Endothelial Growth Factors
ENDOTHELIUM
Endothelium - metabolism
Epitopes
FIBROBLASTS
Fibroblasts - metabolism
Fundamental and applied biological sciences. Psychology
Growth Substances - immunology
Growth Substances - metabolism
HEMATOLOGIC AGENTS
HEPARIN
Heparin - pharmacology
Human umbilical vein endothelial cells
Humans
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MAN
MEMBRANES
MICE
Mitosis
Molecular and cellular biology
MONOCLONAL ANTIBODIES
MUCOPOLYSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
POLYPEPTIDES
POLYSACCHARIDES
PRIMATES
Protein Binding - drug effects
Protein Conformation - drug effects
PROTEINS
RADIOISOTOPES
RADIOLOGY AND NUCLEAR MEDICINE
RADIONUCLIDE KINETICS
RADIORECEPTOR ASSAY
Receptors
Receptors, Mitogen - metabolism
Receptors, Vascular Endothelial Growth Factor
Responses to growth factors, tumor promotors, other factors
RODENTS
SACCHARIDES
SOMATIC CELLS
TISSUES
TRACER TECHNIQUES
Ungulates
VERTEBRATES
title Interaction of Endothelial Cell Growth Factor with Heparin: Characterization by Receptor and Antibody Recognition
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