Thrombopoietin Modulates Platelet Activation in Vitro through Protein‐Tyrosine Phosphorylation
To determine the roles of thrombopoietin (TPO) in platelet function in vitro, we examined the effects of TPO on platelet aggregation. Although several proteins in platelets were tyrosine‐phosphorylated by TPO treatment, TPO alone was unable to induce platelet aggregation. However, the secondary wave...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 1996-07, Vol.14 (4), p.439-444 |
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| creator | Kubota, Yoshitsugu Arai, Takeshi Tanaka, Terukazu Yamaoka, Genji Kiuchi, Hiroyuki Kajikawa, Tatsushi Kawanishi, Koichi Ohnishi, Hiroaki Yamaguchi, Masahiro Takahara, Jiro Irino, Shozo |
| description | To determine the roles of thrombopoietin (TPO) in platelet function in vitro, we examined the effects of TPO on platelet aggregation. Although several proteins in platelets were tyrosine‐phosphorylated by TPO treatment, TPO alone was unable to induce platelet aggregation. However, the secondary wave of platelet aggregation induced by adenosine diphosphate (ADP) was enhanced by TPO in a dose‐dependent manner. TPO in conjunction with ADP augmented tyrosine phosphorylation of platelet proteins, including tyrosine‐phosphorylated proteins induced by TPO alone. Genistein inhibited protein‐tyrosine phosphorylation in platelets induced by TPO with ADP and suppressed TPOenhanced platelet aggregation. Moreover, tyrosine phosphorylation of MAP‐kinases induced by TPO alone and TPO with ADP was consistent with TPO‐enhanced platelet aggregation. These findings in the present study suggest that signal transduction involved in TPO‐enhanced platelet aggregation is mediated in part by tyrosine‐phosphorylated proteins, including MAP‐kinases, in platelets through TPO‐stimulated c‐Mpl, TPO receptor. |
| doi_str_mv | 10.1002/stem.140439 |
| format | Article |
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Although several proteins in platelets were tyrosine‐phosphorylated by TPO treatment, TPO alone was unable to induce platelet aggregation. However, the secondary wave of platelet aggregation induced by adenosine diphosphate (ADP) was enhanced by TPO in a dose‐dependent manner. TPO in conjunction with ADP augmented tyrosine phosphorylation of platelet proteins, including tyrosine‐phosphorylated proteins induced by TPO alone. Genistein inhibited protein‐tyrosine phosphorylation in platelets induced by TPO with ADP and suppressed TPOenhanced platelet aggregation. Moreover, tyrosine phosphorylation of MAP‐kinases induced by TPO alone and TPO with ADP was consistent with TPO‐enhanced platelet aggregation. These findings in the present study suggest that signal transduction involved in TPO‐enhanced platelet aggregation is mediated in part by tyrosine‐phosphorylated proteins, including MAP‐kinases, in platelets through TPO‐stimulated c‐Mpl, TPO receptor.</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.140439</identifier><identifier>PMID: 8843545</identifier><language>eng</language><publisher>Bristol: John Wiley & Sons, Ltd</publisher><subject>Adenosine Diphosphate - pharmacology ; ADP ; Blood Platelets - metabolism ; Blood Platelets - physiology ; Cells, Cultured ; Cytokine receptor ; c‐Mpl ; Genistein ; Humans ; Phosphorylation ; Platelet aggregation ; Platelet Aggregation - drug effects ; Proteins - metabolism ; Thrombopoietin ; Thrombopoietin - pharmacology ; Tyrosine - metabolism ; Tyrosine phosphorylation</subject><ispartof>Stem cells (Dayton, Ohio), 1996-07, Vol.14 (4), p.439-444</ispartof><rights>Copyright © 1996 AlphaMed Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4319-aec58d79214d67fb77d8b846c7a3438b2f9498f30f8f9b70f1420cf67318ea6d3</citedby><cites>FETCH-LOGICAL-c4319-aec58d79214d67fb77d8b846c7a3438b2f9498f30f8f9b70f1420cf67318ea6d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8843545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kubota, Yoshitsugu</creatorcontrib><creatorcontrib>Arai, Takeshi</creatorcontrib><creatorcontrib>Tanaka, Terukazu</creatorcontrib><creatorcontrib>Yamaoka, Genji</creatorcontrib><creatorcontrib>Kiuchi, Hiroyuki</creatorcontrib><creatorcontrib>Kajikawa, Tatsushi</creatorcontrib><creatorcontrib>Kawanishi, Koichi</creatorcontrib><creatorcontrib>Ohnishi, Hiroaki</creatorcontrib><creatorcontrib>Yamaguchi, Masahiro</creatorcontrib><creatorcontrib>Takahara, Jiro</creatorcontrib><creatorcontrib>Irino, Shozo</creatorcontrib><title>Thrombopoietin Modulates Platelet Activation in Vitro through Protein‐Tyrosine Phosphorylation</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>To determine the roles of thrombopoietin (TPO) in platelet function in vitro, we examined the effects of TPO on platelet aggregation. Although several proteins in platelets were tyrosine‐phosphorylated by TPO treatment, TPO alone was unable to induce platelet aggregation. However, the secondary wave of platelet aggregation induced by adenosine diphosphate (ADP) was enhanced by TPO in a dose‐dependent manner. TPO in conjunction with ADP augmented tyrosine phosphorylation of platelet proteins, including tyrosine‐phosphorylated proteins induced by TPO alone. Genistein inhibited protein‐tyrosine phosphorylation in platelets induced by TPO with ADP and suppressed TPOenhanced platelet aggregation. Moreover, tyrosine phosphorylation of MAP‐kinases induced by TPO alone and TPO with ADP was consistent with TPO‐enhanced platelet aggregation. These findings in the present study suggest that signal transduction involved in TPO‐enhanced platelet aggregation is mediated in part by tyrosine‐phosphorylated proteins, including MAP‐kinases, in platelets through TPO‐stimulated c‐Mpl, TPO receptor.</description><subject>Adenosine Diphosphate - pharmacology</subject><subject>ADP</subject><subject>Blood Platelets - metabolism</subject><subject>Blood Platelets - physiology</subject><subject>Cells, Cultured</subject><subject>Cytokine receptor</subject><subject>c‐Mpl</subject><subject>Genistein</subject><subject>Humans</subject><subject>Phosphorylation</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Proteins - metabolism</subject><subject>Thrombopoietin</subject><subject>Thrombopoietin - pharmacology</subject><subject>Tyrosine - metabolism</subject><subject>Tyrosine phosphorylation</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kLtOwzAYhS0EKlCYmJEysaAUO3Zie6yqcpFaUYnAGnKxiVESB9sBZeMReEaehJRGjEznl853jn4dAM4QnCEIgyvrRD1DBBLM98ARCgn3CUdsf7hhFPkh5PwQHFv7CiEiIWMTMGGM4JCER-A5Lo2uM91qJZxqvLUuuip1wnqbrVTCefPcqffUKd14A_CknNGeG1LdS-ltjHZCNd-fX3FvtFWN8Daltm2pTV_9Zk7AgUwrK05HnYLH62W8uPVX9zd3i_nKzwlG3E9FHrKC8gCRIqIyo7RgGSNRTlNMMMsCyQlnEkPJJM8olIgEMJcRxYiJNCrwFFzseluj3zphXVIrm4uqShuhO5tQRhDGlA_g5Q7Mh4etETJpjapT0ycIJts9k-2eyW7PgT4fa7usFsUfOw44-Hjnf6hK9P9VJQ_xcj22_gAlnYQU</recordid><startdate>199607</startdate><enddate>199607</enddate><creator>Kubota, Yoshitsugu</creator><creator>Arai, Takeshi</creator><creator>Tanaka, Terukazu</creator><creator>Yamaoka, Genji</creator><creator>Kiuchi, Hiroyuki</creator><creator>Kajikawa, Tatsushi</creator><creator>Kawanishi, Koichi</creator><creator>Ohnishi, Hiroaki</creator><creator>Yamaguchi, Masahiro</creator><creator>Takahara, Jiro</creator><creator>Irino, Shozo</creator><general>John Wiley & Sons, Ltd</general><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>199607</creationdate><title>Thrombopoietin Modulates Platelet Activation in Vitro through Protein‐Tyrosine Phosphorylation</title><author>Kubota, Yoshitsugu ; Arai, Takeshi ; Tanaka, Terukazu ; Yamaoka, Genji ; Kiuchi, Hiroyuki ; Kajikawa, Tatsushi ; Kawanishi, Koichi ; Ohnishi, Hiroaki ; Yamaguchi, Masahiro ; Takahara, Jiro ; Irino, Shozo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4319-aec58d79214d67fb77d8b846c7a3438b2f9498f30f8f9b70f1420cf67318ea6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adenosine Diphosphate - pharmacology</topic><topic>ADP</topic><topic>Blood Platelets - metabolism</topic><topic>Blood Platelets - physiology</topic><topic>Cells, Cultured</topic><topic>Cytokine receptor</topic><topic>c‐Mpl</topic><topic>Genistein</topic><topic>Humans</topic><topic>Phosphorylation</topic><topic>Platelet aggregation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Proteins - metabolism</topic><topic>Thrombopoietin</topic><topic>Thrombopoietin - pharmacology</topic><topic>Tyrosine - metabolism</topic><topic>Tyrosine phosphorylation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kubota, Yoshitsugu</creatorcontrib><creatorcontrib>Arai, Takeshi</creatorcontrib><creatorcontrib>Tanaka, Terukazu</creatorcontrib><creatorcontrib>Yamaoka, Genji</creatorcontrib><creatorcontrib>Kiuchi, Hiroyuki</creatorcontrib><creatorcontrib>Kajikawa, Tatsushi</creatorcontrib><creatorcontrib>Kawanishi, Koichi</creatorcontrib><creatorcontrib>Ohnishi, Hiroaki</creatorcontrib><creatorcontrib>Yamaguchi, Masahiro</creatorcontrib><creatorcontrib>Takahara, Jiro</creatorcontrib><creatorcontrib>Irino, Shozo</creatorcontrib><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>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kubota, Yoshitsugu</au><au>Arai, Takeshi</au><au>Tanaka, Terukazu</au><au>Yamaoka, Genji</au><au>Kiuchi, Hiroyuki</au><au>Kajikawa, Tatsushi</au><au>Kawanishi, Koichi</au><au>Ohnishi, Hiroaki</au><au>Yamaguchi, Masahiro</au><au>Takahara, Jiro</au><au>Irino, Shozo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thrombopoietin Modulates Platelet Activation in Vitro through Protein‐Tyrosine Phosphorylation</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>1996-07</date><risdate>1996</risdate><volume>14</volume><issue>4</issue><spage>439</spage><epage>444</epage><pages>439-444</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>To determine the roles of thrombopoietin (TPO) in platelet function in vitro, we examined the effects of TPO on platelet aggregation. Although several proteins in platelets were tyrosine‐phosphorylated by TPO treatment, TPO alone was unable to induce platelet aggregation. However, the secondary wave of platelet aggregation induced by adenosine diphosphate (ADP) was enhanced by TPO in a dose‐dependent manner. TPO in conjunction with ADP augmented tyrosine phosphorylation of platelet proteins, including tyrosine‐phosphorylated proteins induced by TPO alone. Genistein inhibited protein‐tyrosine phosphorylation in platelets induced by TPO with ADP and suppressed TPOenhanced platelet aggregation. Moreover, tyrosine phosphorylation of MAP‐kinases induced by TPO alone and TPO with ADP was consistent with TPO‐enhanced platelet aggregation. These findings in the present study suggest that signal transduction involved in TPO‐enhanced platelet aggregation is mediated in part by tyrosine‐phosphorylated proteins, including MAP‐kinases, in platelets through TPO‐stimulated c‐Mpl, TPO receptor.</abstract><cop>Bristol</cop><pub>John Wiley & Sons, Ltd</pub><pmid>8843545</pmid><doi>10.1002/stem.140439</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Stem cells (Dayton, Ohio), 1996-07, Vol.14 (4), p.439-444 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Adenosine Diphosphate - pharmacology ADP Blood Platelets - metabolism Blood Platelets - physiology Cells, Cultured Cytokine receptor c‐Mpl Genistein Humans Phosphorylation Platelet aggregation Platelet Aggregation - drug effects Proteins - metabolism Thrombopoietin Thrombopoietin - pharmacology Tyrosine - metabolism Tyrosine phosphorylation |
| title | Thrombopoietin Modulates Platelet Activation in Vitro through Protein‐Tyrosine Phosphorylation |
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