Opposing Effects of Low and High Molecular Weight Kininogens on Cell Adhesion

High molecular weight kininogen (HK) blocks cell spreading but not cell attachment to surfaces coated with vitronectin and other ligands of β3 integrins. We sought to learn the structural basis of this phenomenon. Monoclonal antibodies against the histidine-rich D5 domain in the light chain of 2-cha...

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Veröffentlicht in:Journal of biochemistry (Tokyo) 1998-09, Vol.124 (3), p.473-484
Hauptverfasser: Asakura, Shinji, Yang, Wei, Sottile, Jane, Zhang, Qinghong, Jin, Yong-ming, Ohkubo, Iwao, Sasaki, Makoto, Matsuda, Michio, Hirata, Hajime, Mosher, Deane F.
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container_end_page 484
container_issue 3
container_start_page 473
container_title Journal of biochemistry (Tokyo)
container_volume 124
creator Asakura, Shinji
Yang, Wei
Sottile, Jane
Zhang, Qinghong
Jin, Yong-ming
Ohkubo, Iwao
Sasaki, Makoto
Matsuda, Michio
Hirata, Hajime
Mosher, Deane F.
description High molecular weight kininogen (HK) blocks cell spreading but not cell attachment to surfaces coated with vitronectin and other ligands of β3 integrins. We sought to learn the structural basis of this phenomenon. Monoclonal antibodies against the histidine-rich D5 domain in the light chain of 2-chain HK abolished the inhibitory effect of 2-chain HK on spreading of MG-63 osteosarcoma cells on vitronectin-coated tissue-culture plastic. The antibodies were effective only if incubated with 2-chain HK in solution and did not abolish the anti-cell-spreading effect of 2-chain HK that was pre-adsorbed to tissue-culture plastic. Exposure of an epitope in the histidine-rich domain was less when HK was adsorbed to tissue-culture plastic (oxidized polystyrene) than when it was adsorbed to ELISA plastic (untreated polystyrene). Loss of the epitope correlated with increased anti-cell-spreading activity of HK on tissue-culture plastic. The light chain of 2-chain HK containing D5 and that containing recombinant D5 both had anti-cell-spreading activity, but only when present in solution during adhesion assays. Pre-adsorption of recombinant D5 to tissue-culture plastic resulted in a surface on which adsorbed 2-chain HK had little anti-cellspreading activity. Binding study revealed that HKa bound to immobilized vitronectin. The histidine-rich D5 domain of light chain of HK was identified as one of the binding sites of vitronectin, suggesting that the masking of the RGD cell-binding site of immobilized vitronectin is the molecular mechanism of anti-cell-spreading effect of HKa. In contrast, low molecular weight kininogen (LK), which lacks D5, augmented cell spreading on vitronectin-coated tissue-culture plastic. Thus, HK and LK have opposing effects on VN-dependent cell adhesion. The augmenting effect of LK was greater if LK was preincubated with cells or adsorbed to the surface at pH>7.0. Analysis of fragments of LK and antibody inhibition studies localized the cell-adhesion activity to the D3 domain that is common to LK and HK. These findings indicate that the D5 domain mediates the adsorption of HK or 2-chain HK to vitronectin substratum in anti-adhesive conformations, i.e., masking of the RGD cell-binding site of vitronectin. Such conformers inhibit cell spreading on vitronectin even though a cell-adhesion site is present in D3.
doi_str_mv 10.1093/oxfordjournals.jbchem.a022138
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We sought to learn the structural basis of this phenomenon. Monoclonal antibodies against the histidine-rich D5 domain in the light chain of 2-chain HK abolished the inhibitory effect of 2-chain HK on spreading of MG-63 osteosarcoma cells on vitronectin-coated tissue-culture plastic. The antibodies were effective only if incubated with 2-chain HK in solution and did not abolish the anti-cell-spreading effect of 2-chain HK that was pre-adsorbed to tissue-culture plastic. Exposure of an epitope in the histidine-rich domain was less when HK was adsorbed to tissue-culture plastic (oxidized polystyrene) than when it was adsorbed to ELISA plastic (untreated polystyrene). Loss of the epitope correlated with increased anti-cell-spreading activity of HK on tissue-culture plastic. The light chain of 2-chain HK containing D5 and that containing recombinant D5 both had anti-cell-spreading activity, but only when present in solution during adhesion assays. Pre-adsorption of recombinant D5 to tissue-culture plastic resulted in a surface on which adsorbed 2-chain HK had little anti-cellspreading activity. Binding study revealed that HKa bound to immobilized vitronectin. The histidine-rich D5 domain of light chain of HK was identified as one of the binding sites of vitronectin, suggesting that the masking of the RGD cell-binding site of immobilized vitronectin is the molecular mechanism of anti-cell-spreading effect of HKa. In contrast, low molecular weight kininogen (LK), which lacks D5, augmented cell spreading on vitronectin-coated tissue-culture plastic. Thus, HK and LK have opposing effects on VN-dependent cell adhesion. The augmenting effect of LK was greater if LK was preincubated with cells or adsorbed to the surface at pH&gt;7.0. Analysis of fragments of LK and antibody inhibition studies localized the cell-adhesion activity to the D3 domain that is common to LK and HK. 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Pre-adsorption of recombinant D5 to tissue-culture plastic resulted in a surface on which adsorbed 2-chain HK had little anti-cellspreading activity. Binding study revealed that HKa bound to immobilized vitronectin. The histidine-rich D5 domain of light chain of HK was identified as one of the binding sites of vitronectin, suggesting that the masking of the RGD cell-binding site of immobilized vitronectin is the molecular mechanism of anti-cell-spreading effect of HKa. In contrast, low molecular weight kininogen (LK), which lacks D5, augmented cell spreading on vitronectin-coated tissue-culture plastic. Thus, HK and LK have opposing effects on VN-dependent cell adhesion. The augmenting effect of LK was greater if LK was preincubated with cells or adsorbed to the surface at pH&gt;7.0. Analysis of fragments of LK and antibody inhibition studies localized the cell-adhesion activity to the D3 domain that is common to LK and HK. These findings indicate that the D5 domain mediates the adsorption of HK or 2-chain HK to vitronectin substratum in anti-adhesive conformations, i.e., masking of the RGD cell-binding site of vitronectin. Such conformers inhibit cell spreading on vitronectin even though a cell-adhesion site is present in D3.</description><subject>anti-cell-adhesion</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Base Sequence</subject><subject>Cell Adhesion - physiology</subject><subject>Cell Movement - immunology</subject><subject>DNA Primers</subject><subject>high molecular weight kininogen</subject><subject>histidine rich domain</subject><subject>Humans</subject><subject>Kininogens - chemistry</subject><subject>Kininogens - immunology</subject><subject>Kininogens - physiology</subject><subject>low molecular weight kininogen</subject><subject>Molecular Weight</subject><subject>Tumor Cells, Cultured</subject><subject>Vitronectin</subject><subject>Vitronectin - physiology</subject><issn>0021-924X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtPwzAQhH0AledPQPIFbil-JE5y4IAiSoFWvRQVcbEcx25TErvYiYB_j1GqSpxWq5nZHX0AXGM0xiint_ZbW1dtbe-MaPx4W8qNascCEYJpdgROESI4ykn8dgLOvN_-rYTSERjlKSEsSU7BfLHbWV-bNXzQWsnOQ6vhzH5BYSo4rdcbOLeNkn0jHFypsHfwpTa1sWtlgtfAQjUNvK82ytfWXIBjHYqoy_08B6-Th2UxjWaLx6fifhbJOMm6qBRZphAKXZhkrGQZFoRQQfJYY0wJrdIqKUstiE5lViaISB0HSZesynWMND0HN8PdnbOfvfIdb2svQxNhlO09T2mWZgmNg_FuMEpnvXdK852rW-F-OEb8DyH_j5APCPkeYchf7R_1ZauqQ3rPL-jRoNe-U98HWbgPzlKaJnz69s7xkhVs9TzhBf0FCICGIw</recordid><startdate>19980901</startdate><enddate>19980901</enddate><creator>Asakura, Shinji</creator><creator>Yang, Wei</creator><creator>Sottile, Jane</creator><creator>Zhang, Qinghong</creator><creator>Jin, Yong-ming</creator><creator>Ohkubo, Iwao</creator><creator>Sasaki, Makoto</creator><creator>Matsuda, Michio</creator><creator>Hirata, Hajime</creator><creator>Mosher, Deane F.</creator><general>Oxford University Press</general><scope>BSCLL</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></search><sort><creationdate>19980901</creationdate><title>Opposing Effects of Low and High Molecular Weight Kininogens on Cell Adhesion</title><author>Asakura, Shinji ; Yang, Wei ; Sottile, Jane ; Zhang, Qinghong ; Jin, Yong-ming ; Ohkubo, Iwao ; Sasaki, Makoto ; Matsuda, Michio ; Hirata, Hajime ; Mosher, Deane F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-ba88e001236c66b681a223a294f11323d7d5bbfa2f7c8b502cf44f1fb6d9f40f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>anti-cell-adhesion</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Base Sequence</topic><topic>Cell Adhesion - physiology</topic><topic>Cell Movement - immunology</topic><topic>DNA Primers</topic><topic>high molecular weight kininogen</topic><topic>histidine rich domain</topic><topic>Humans</topic><topic>Kininogens - chemistry</topic><topic>Kininogens - immunology</topic><topic>Kininogens - physiology</topic><topic>low molecular weight kininogen</topic><topic>Molecular Weight</topic><topic>Tumor Cells, Cultured</topic><topic>Vitronectin</topic><topic>Vitronectin - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asakura, Shinji</creatorcontrib><creatorcontrib>Yang, Wei</creatorcontrib><creatorcontrib>Sottile, Jane</creatorcontrib><creatorcontrib>Zhang, Qinghong</creatorcontrib><creatorcontrib>Jin, Yong-ming</creatorcontrib><creatorcontrib>Ohkubo, Iwao</creatorcontrib><creatorcontrib>Sasaki, Makoto</creatorcontrib><creatorcontrib>Matsuda, Michio</creatorcontrib><creatorcontrib>Hirata, Hajime</creatorcontrib><creatorcontrib>Mosher, Deane F.</creatorcontrib><collection>Istex</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><jtitle>Journal of biochemistry (Tokyo)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Asakura, Shinji</au><au>Yang, Wei</au><au>Sottile, Jane</au><au>Zhang, Qinghong</au><au>Jin, Yong-ming</au><au>Ohkubo, Iwao</au><au>Sasaki, Makoto</au><au>Matsuda, Michio</au><au>Hirata, Hajime</au><au>Mosher, Deane F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Opposing Effects of Low and High Molecular Weight Kininogens on Cell Adhesion</atitle><jtitle>Journal of biochemistry (Tokyo)</jtitle><addtitle>J Biochem</addtitle><date>1998-09-01</date><risdate>1998</risdate><volume>124</volume><issue>3</issue><spage>473</spage><epage>484</epage><pages>473-484</pages><issn>0021-924X</issn><abstract>High molecular weight kininogen (HK) blocks cell spreading but not cell attachment to surfaces coated with vitronectin and other ligands of β3 integrins. We sought to learn the structural basis of this phenomenon. Monoclonal antibodies against the histidine-rich D5 domain in the light chain of 2-chain HK abolished the inhibitory effect of 2-chain HK on spreading of MG-63 osteosarcoma cells on vitronectin-coated tissue-culture plastic. The antibodies were effective only if incubated with 2-chain HK in solution and did not abolish the anti-cell-spreading effect of 2-chain HK that was pre-adsorbed to tissue-culture plastic. Exposure of an epitope in the histidine-rich domain was less when HK was adsorbed to tissue-culture plastic (oxidized polystyrene) than when it was adsorbed to ELISA plastic (untreated polystyrene). Loss of the epitope correlated with increased anti-cell-spreading activity of HK on tissue-culture plastic. The light chain of 2-chain HK containing D5 and that containing recombinant D5 both had anti-cell-spreading activity, but only when present in solution during adhesion assays. Pre-adsorption of recombinant D5 to tissue-culture plastic resulted in a surface on which adsorbed 2-chain HK had little anti-cellspreading activity. Binding study revealed that HKa bound to immobilized vitronectin. The histidine-rich D5 domain of light chain of HK was identified as one of the binding sites of vitronectin, suggesting that the masking of the RGD cell-binding site of immobilized vitronectin is the molecular mechanism of anti-cell-spreading effect of HKa. In contrast, low molecular weight kininogen (LK), which lacks D5, augmented cell spreading on vitronectin-coated tissue-culture plastic. Thus, HK and LK have opposing effects on VN-dependent cell adhesion. The augmenting effect of LK was greater if LK was preincubated with cells or adsorbed to the surface at pH&gt;7.0. Analysis of fragments of LK and antibody inhibition studies localized the cell-adhesion activity to the D3 domain that is common to LK and HK. These findings indicate that the D5 domain mediates the adsorption of HK or 2-chain HK to vitronectin substratum in anti-adhesive conformations, i.e., masking of the RGD cell-binding site of vitronectin. Such conformers inhibit cell spreading on vitronectin even though a cell-adhesion site is present in D3.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>9722655</pmid><doi>10.1093/oxfordjournals.jbchem.a022138</doi><tpages>12</tpages></addata></record>
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subjects anti-cell-adhesion
Antibodies, Monoclonal - immunology
Base Sequence
Cell Adhesion - physiology
Cell Movement - immunology
DNA Primers
high molecular weight kininogen
histidine rich domain
Humans
Kininogens - chemistry
Kininogens - immunology
Kininogens - physiology
low molecular weight kininogen
Molecular Weight
Tumor Cells, Cultured
Vitronectin
Vitronectin - physiology
title Opposing Effects of Low and High Molecular Weight Kininogens on Cell Adhesion
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