ADAM-9 Is an Insulin-like Growth Factor Binding Protein-5 Protease Produced and Secreted by Human Osteoblasts
IGF binding protein-5 (BP-5) is an important bone formation regulator. Therefore, elucidation of the identity of IGF binding protein-5 (BP-5) protease produced by osteoblasts is important for our understanding of the molecular pathways that control the action of BP-5. In this regard, BP-5 protease p...
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Veröffentlicht in: | Biochemistry (Easton) 2002-12, Vol.41 (51), p.15394-15403 |
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description | IGF binding protein-5 (BP-5) is an important bone formation regulator. Therefore, elucidation of the identity of IGF binding protein-5 (BP-5) protease produced by osteoblasts is important for our understanding of the molecular pathways that control the action of BP-5. In this regard, BP-5 protease purified by various chromatographic steps from a conditioned medium of U2 human osteosarcoma cells migrated as a single major band, which comigrated with the protease activity in native PAGE and yielded multiple bands in SDS−PAGE under reducing conditions. N-Terminal sequencing of these bands revealed that three of the bands yielded amino acid sequences that were identical to that of α2 macroglobulin (α2M). Although α2M was produced by human osteoblasts (OBs), it was not found to be a BP-5 protease. Because α2M had been shown to complex with ADAM proteases and because ADAM-12 was found to cleave BP-3 and BP-5, we evaluated if one of the members of ADAM family was the BP-5 protease. On the basis of the findings that (1) purified preparations of BP-5 protease from U2 cell CM contained ADAM-9, (2) ADAM-9 is produced and secreted in high abundance by various human OB cell types, (3) purified ADAM-9 cleaved BP-5 effectively while it did not cleave other IGFBPs or did so with less potency, and (4) purified ADAM-9 bound to α2M, we conclude that ADAM-9 is a BP-5 protease produced by human OBs. |
doi_str_mv | 10.1021/bi026458q |
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Therefore, elucidation of the identity of IGF binding protein-5 (BP-5) protease produced by osteoblasts is important for our understanding of the molecular pathways that control the action of BP-5. In this regard, BP-5 protease purified by various chromatographic steps from a conditioned medium of U2 human osteosarcoma cells migrated as a single major band, which comigrated with the protease activity in native PAGE and yielded multiple bands in SDS−PAGE under reducing conditions. N-Terminal sequencing of these bands revealed that three of the bands yielded amino acid sequences that were identical to that of α2 macroglobulin (α2M). Although α2M was produced by human osteoblasts (OBs), it was not found to be a BP-5 protease. Because α2M had been shown to complex with ADAM proteases and because ADAM-12 was found to cleave BP-3 and BP-5, we evaluated if one of the members of ADAM family was the BP-5 protease. On the basis of the findings that (1) purified preparations of BP-5 protease from U2 cell CM contained ADAM-9, (2) ADAM-9 is produced and secreted in high abundance by various human OB cell types, (3) purified ADAM-9 cleaved BP-5 effectively while it did not cleave other IGFBPs or did so with less potency, and (4) purified ADAM-9 bound to α2M, we conclude that ADAM-9 is a BP-5 protease produced by human OBs.</description><identifier>ISSN: 0006-2960</identifier><identifier>EISSN: 1520-4995</identifier><identifier>DOI: 10.1021/bi026458q</identifier><identifier>PMID: 12484779</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>ADAM Proteins ; alpha-Macroglobulins - biosynthesis ; alpha-Macroglobulins - chemistry ; Cell Line, Transformed ; Cells, Cultured ; Disintegrins ; Electrophoresis, Polyacrylamide Gel ; Humans ; Insulin-Like Growth Factor Binding Protein 5 - metabolism ; meltrin-^g ; Membrane Proteins - biosynthesis ; Membrane Proteins - chemistry ; Membrane Proteins - isolation & purification ; Membrane Proteins - metabolism ; Metalloendopeptidases - biosynthesis ; Metalloendopeptidases - chemistry ; Metalloendopeptidases - isolation & purification ; Metalloendopeptidases - metabolism ; Muscle Proteins - biosynthesis ; Muscle Proteins - chemistry ; Muscle Proteins - isolation & purification ; Muscle Proteins - metabolism ; Osteoblasts - enzymology ; Osteoblasts - metabolism ; Peptide Fragments - chemistry ; Peptide Fragments - isolation & purification ; Protein Binding ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - chemistry ; Recombinant Proteins - isolation & purification ; Sequence Analysis, Protein ; Substrate Specificity ; Tumor Cells, Cultured</subject><ispartof>Biochemistry (Easton), 2002-12, Vol.41 (51), p.15394-15403</ispartof><rights>Copyright © 2002 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a380t-dc750c3e01ad8f543f0031c5b1606439b318922aeac801d105e7dbb427516d443</citedby><cites>FETCH-LOGICAL-a380t-dc750c3e01ad8f543f0031c5b1606439b318922aeac801d105e7dbb427516d443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bi026458q$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bi026458q$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12484779$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohan, Subburaman</creatorcontrib><creatorcontrib>Thompson, Garrett R</creatorcontrib><creatorcontrib>Amaar, Yousef G</creatorcontrib><creatorcontrib>Hathaway, Gary</creatorcontrib><creatorcontrib>Tschesche, Harald</creatorcontrib><creatorcontrib>Baylink, David J</creatorcontrib><title>ADAM-9 Is an Insulin-like Growth Factor Binding Protein-5 Protease Produced and Secreted by Human Osteoblasts</title><title>Biochemistry (Easton)</title><addtitle>Biochemistry</addtitle><description>IGF binding protein-5 (BP-5) is an important bone formation regulator. Therefore, elucidation of the identity of IGF binding protein-5 (BP-5) protease produced by osteoblasts is important for our understanding of the molecular pathways that control the action of BP-5. In this regard, BP-5 protease purified by various chromatographic steps from a conditioned medium of U2 human osteosarcoma cells migrated as a single major band, which comigrated with the protease activity in native PAGE and yielded multiple bands in SDS−PAGE under reducing conditions. N-Terminal sequencing of these bands revealed that three of the bands yielded amino acid sequences that were identical to that of α2 macroglobulin (α2M). Although α2M was produced by human osteoblasts (OBs), it was not found to be a BP-5 protease. Because α2M had been shown to complex with ADAM proteases and because ADAM-12 was found to cleave BP-3 and BP-5, we evaluated if one of the members of ADAM family was the BP-5 protease. On the basis of the findings that (1) purified preparations of BP-5 protease from U2 cell CM contained ADAM-9, (2) ADAM-9 is produced and secreted in high abundance by various human OB cell types, (3) purified ADAM-9 cleaved BP-5 effectively while it did not cleave other IGFBPs or did so with less potency, and (4) purified ADAM-9 bound to α2M, we conclude that ADAM-9 is a BP-5 protease produced by human OBs.</description><subject>ADAM Proteins</subject><subject>alpha-Macroglobulins - biosynthesis</subject><subject>alpha-Macroglobulins - chemistry</subject><subject>Cell Line, Transformed</subject><subject>Cells, Cultured</subject><subject>Disintegrins</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Humans</subject><subject>Insulin-Like Growth Factor Binding Protein 5 - metabolism</subject><subject>meltrin-^g</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Membrane Proteins - chemistry</subject><subject>Membrane Proteins - isolation & purification</subject><subject>Membrane Proteins - metabolism</subject><subject>Metalloendopeptidases - biosynthesis</subject><subject>Metalloendopeptidases - chemistry</subject><subject>Metalloendopeptidases - isolation & purification</subject><subject>Metalloendopeptidases - metabolism</subject><subject>Muscle Proteins - biosynthesis</subject><subject>Muscle Proteins - chemistry</subject><subject>Muscle Proteins - isolation & purification</subject><subject>Muscle Proteins - metabolism</subject><subject>Osteoblasts - enzymology</subject><subject>Osteoblasts - metabolism</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptide Fragments - isolation & purification</subject><subject>Protein Binding</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Recombinant Proteins - chemistry</subject><subject>Recombinant Proteins - isolation & purification</subject><subject>Sequence Analysis, Protein</subject><subject>Substrate Specificity</subject><subject>Tumor Cells, Cultured</subject><issn>0006-2960</issn><issn>1520-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1PGzEQhq2KCkLKoX-g8qWVOGw7_lqvjyElJBJVaKFny2s7dGE_wN4V5N_jaCO4VOLkGfnRM5p3EPpM4DsBSn6UFdCci-LxA5oQQSHjSokDNAGAPKMqhyN0HONdajlIfoiOCOUFl1JNUDP7OfuVKbyK2LR41cahrtqsru49vgjdU_8PL4ztu4DPqtZV7S2-Cl3vEyLGykS_K9xgvUsGh6-9Db5PTbnFy6FJ0nXsfVfWJvbxE_q4MXX0J_t3iv4uzm_my-xyfbGazy4zwwroM2elAMs8EOOKjeBsA8CIFSXJIedMlYwUilLjjS2AOALCS1eWnEpBcsc5m6Jvo_chdI-Dj71uqmh9XZvWd0PUkqbliaLvgrs5wNnOeDqCNnQxBr_RD6FqTNhqAnp3BP16hMR-2UuHsvHujdynnoBsBKoUzfPrvwn3OpdMCn1zda1__1ksC5UzfZb4ryNvbNR33RDaFN5_Br8AwaGa5Q</recordid><startdate>20021224</startdate><enddate>20021224</enddate><creator>Mohan, Subburaman</creator><creator>Thompson, Garrett R</creator><creator>Amaar, Yousef G</creator><creator>Hathaway, Gary</creator><creator>Tschesche, Harald</creator><creator>Baylink, David J</creator><general>American Chemical Society</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>7QP</scope><scope>7X8</scope></search><sort><creationdate>20021224</creationdate><title>ADAM-9 Is an Insulin-like Growth Factor Binding Protein-5 Protease Produced and Secreted by Human Osteoblasts</title><author>Mohan, Subburaman ; Thompson, Garrett R ; Amaar, Yousef G ; Hathaway, Gary ; Tschesche, Harald ; Baylink, David J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a380t-dc750c3e01ad8f543f0031c5b1606439b318922aeac801d105e7dbb427516d443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>ADAM Proteins</topic><topic>alpha-Macroglobulins - biosynthesis</topic><topic>alpha-Macroglobulins - chemistry</topic><topic>Cell Line, Transformed</topic><topic>Cells, Cultured</topic><topic>Disintegrins</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Humans</topic><topic>Insulin-Like Growth Factor Binding Protein 5 - metabolism</topic><topic>meltrin-^g</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Membrane Proteins - chemistry</topic><topic>Membrane Proteins - isolation & purification</topic><topic>Membrane Proteins - metabolism</topic><topic>Metalloendopeptidases - biosynthesis</topic><topic>Metalloendopeptidases - chemistry</topic><topic>Metalloendopeptidases - isolation & purification</topic><topic>Metalloendopeptidases - metabolism</topic><topic>Muscle Proteins - biosynthesis</topic><topic>Muscle Proteins - chemistry</topic><topic>Muscle Proteins - isolation & purification</topic><topic>Muscle Proteins - metabolism</topic><topic>Osteoblasts - enzymology</topic><topic>Osteoblasts - metabolism</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptide Fragments - isolation & purification</topic><topic>Protein Binding</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Recombinant Proteins - chemistry</topic><topic>Recombinant Proteins - isolation & purification</topic><topic>Sequence Analysis, Protein</topic><topic>Substrate Specificity</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mohan, Subburaman</creatorcontrib><creatorcontrib>Thompson, Garrett R</creatorcontrib><creatorcontrib>Amaar, Yousef G</creatorcontrib><creatorcontrib>Hathaway, Gary</creatorcontrib><creatorcontrib>Tschesche, Harald</creatorcontrib><creatorcontrib>Baylink, David J</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>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemistry (Easton)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mohan, Subburaman</au><au>Thompson, Garrett R</au><au>Amaar, Yousef G</au><au>Hathaway, Gary</au><au>Tschesche, Harald</au><au>Baylink, David J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ADAM-9 Is an Insulin-like Growth Factor Binding Protein-5 Protease Produced and Secreted by Human Osteoblasts</atitle><jtitle>Biochemistry (Easton)</jtitle><addtitle>Biochemistry</addtitle><date>2002-12-24</date><risdate>2002</risdate><volume>41</volume><issue>51</issue><spage>15394</spage><epage>15403</epage><pages>15394-15403</pages><issn>0006-2960</issn><eissn>1520-4995</eissn><abstract>IGF binding protein-5 (BP-5) is an important bone formation regulator. Therefore, elucidation of the identity of IGF binding protein-5 (BP-5) protease produced by osteoblasts is important for our understanding of the molecular pathways that control the action of BP-5. In this regard, BP-5 protease purified by various chromatographic steps from a conditioned medium of U2 human osteosarcoma cells migrated as a single major band, which comigrated with the protease activity in native PAGE and yielded multiple bands in SDS−PAGE under reducing conditions. N-Terminal sequencing of these bands revealed that three of the bands yielded amino acid sequences that were identical to that of α2 macroglobulin (α2M). Although α2M was produced by human osteoblasts (OBs), it was not found to be a BP-5 protease. Because α2M had been shown to complex with ADAM proteases and because ADAM-12 was found to cleave BP-3 and BP-5, we evaluated if one of the members of ADAM family was the BP-5 protease. On the basis of the findings that (1) purified preparations of BP-5 protease from U2 cell CM contained ADAM-9, (2) ADAM-9 is produced and secreted in high abundance by various human OB cell types, (3) purified ADAM-9 cleaved BP-5 effectively while it did not cleave other IGFBPs or did so with less potency, and (4) purified ADAM-9 bound to α2M, we conclude that ADAM-9 is a BP-5 protease produced by human OBs.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>12484779</pmid><doi>10.1021/bi026458q</doi><tpages>10</tpages></addata></record> |
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subjects | ADAM Proteins alpha-Macroglobulins - biosynthesis alpha-Macroglobulins - chemistry Cell Line, Transformed Cells, Cultured Disintegrins Electrophoresis, Polyacrylamide Gel Humans Insulin-Like Growth Factor Binding Protein 5 - metabolism meltrin-^g Membrane Proteins - biosynthesis Membrane Proteins - chemistry Membrane Proteins - isolation & purification Membrane Proteins - metabolism Metalloendopeptidases - biosynthesis Metalloendopeptidases - chemistry Metalloendopeptidases - isolation & purification Metalloendopeptidases - metabolism Muscle Proteins - biosynthesis Muscle Proteins - chemistry Muscle Proteins - isolation & purification Muscle Proteins - metabolism Osteoblasts - enzymology Osteoblasts - metabolism Peptide Fragments - chemistry Peptide Fragments - isolation & purification Protein Binding Recombinant Proteins - biosynthesis Recombinant Proteins - chemistry Recombinant Proteins - isolation & purification Sequence Analysis, Protein Substrate Specificity Tumor Cells, Cultured |
title | ADAM-9 Is an Insulin-like Growth Factor Binding Protein-5 Protease Produced and Secreted by Human Osteoblasts |
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