Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism
The hematopoietic-specific Gα16 protein has recently been shown to mediate receptor-induced activation of the signal transducer and activator of transcription 3 (STAT3). In the present study, we have delineated the mechanism by which Gα16 stimulates STAT3 in human embryonic kidney 293 cells. A const...
Gespeichert in:
Veröffentlicht in: | The Journal of biological chemistry 2003-12, Vol.278 (52), p.52154-52165 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 52165 |
---|---|
container_issue | 52 |
container_start_page | 52154 |
container_title | The Journal of biological chemistry |
container_volume | 278 |
creator | Lo, Rico K.H. Cheung, Helen Wong, Yung H. |
description | The hematopoietic-specific Gα16 protein has recently been shown to mediate receptor-induced activation of the signal transducer and activator of transcription 3 (STAT3). In the present study, we have delineated the mechanism by which Gα16 stimulates STAT3 in human embryonic kidney 293 cells. A constitutively active Gα16 mutant, Gα16QL, stimulated STAT3-dependent luciferase activity as well as the phosphorylation of STAT3 at both Tyr705 and Ser727. Gα16QL-induced STAT3 activation was enhanced by overexpression of extracellular signal-regulated kinase 1 (ERK1), but was inhibited by U0126, a Raf-1 inhibitor, and coexpression of the dominant negative mutants of Ras and Rac1. Inhibition of phospholipase Cβ, protein kinase C, and calmodulin-dependent kinase II by their respective inhibitors also suppressed Gα16QL-induced STAT3 activation. The involvement of tyrosine kinases such as c-Src and Janus kinase 2 and 3 (JAK2 and JAK3) in Gα16QL-induced activation of STAT3 was illustrated by the combined use of selective inhibitors and dominant negative mutants. In contrast, c-Jun N-terminal kinase, p38 MAPK, RhoA, Cdc42, phosphatidylinositol 3-kinase, and the epidermal growth factor receptor did not appear to be required. Similar observations were obtained with human erythroleukemia cells, where STAT3 phosphorylation was stimulated by C5a in a PTX-insensitive manner. Collectively, these results highlight the important regulatory roles of the Ras/Raf/MEK/ERK and c-Src/JAK pathways on the stimulation of STAT3 by activated Gα16. Demonstration of the involvement of different kinases in Gα16QL-induced STAT3 activation supports the involvement of multiple signaling pathways in the regulation of transcription by G proteins. |
doi_str_mv | 10.1074/jbc.M307299200 |
format | Article |
fullrecord | <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1074_jbc_M307299200</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925820752178</els_id><sourcerecordid>S0021925820752178</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3070-4415c8a3444566eb09c375ca5406448ee225299a4ab01ab9bb215abcfdd2ed563</originalsourceid><addsrcrecordid>eNp1kMtOAjEUhhujiYhuXfcFCr0OM8sJQVQgJoKJrppeDrEEBtIWEh7LF_GZHIKJK8_mnM335z8fQveM9hgdyP7Kut5M0AGvKk7pBeowWgoiFHu_RB1KOSMVV-U1uklpRduRFeugj-G2STnkfQ4HWB9x7U4HHn9_sQLPc9js1yZDwvNFvRD4EAw22JF5dP3nekKwaTwevU6Ihx00HpqMZ-A-TRPS5hZdLc06wd3v7qK3h9Fi-EimL-OnYT0lru1KiZRMudIIKaUqCrC0cmKgnFGSFlKWAJyr9iMjjaXM2MpazpSxbuk9B68K0UW9c66L25QiLPUuho2JR82oPonRrRj9J6YFyjMAbatDgKiTC9A48CGCy9pvw3_oD34eaEE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism</title><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Lo, Rico K.H. ; Cheung, Helen ; Wong, Yung H.</creator><creatorcontrib>Lo, Rico K.H. ; Cheung, Helen ; Wong, Yung H.</creatorcontrib><description>The hematopoietic-specific Gα16 protein has recently been shown to mediate receptor-induced activation of the signal transducer and activator of transcription 3 (STAT3). In the present study, we have delineated the mechanism by which Gα16 stimulates STAT3 in human embryonic kidney 293 cells. A constitutively active Gα16 mutant, Gα16QL, stimulated STAT3-dependent luciferase activity as well as the phosphorylation of STAT3 at both Tyr705 and Ser727. Gα16QL-induced STAT3 activation was enhanced by overexpression of extracellular signal-regulated kinase 1 (ERK1), but was inhibited by U0126, a Raf-1 inhibitor, and coexpression of the dominant negative mutants of Ras and Rac1. Inhibition of phospholipase Cβ, protein kinase C, and calmodulin-dependent kinase II by their respective inhibitors also suppressed Gα16QL-induced STAT3 activation. The involvement of tyrosine kinases such as c-Src and Janus kinase 2 and 3 (JAK2 and JAK3) in Gα16QL-induced activation of STAT3 was illustrated by the combined use of selective inhibitors and dominant negative mutants. In contrast, c-Jun N-terminal kinase, p38 MAPK, RhoA, Cdc42, phosphatidylinositol 3-kinase, and the epidermal growth factor receptor did not appear to be required. Similar observations were obtained with human erythroleukemia cells, where STAT3 phosphorylation was stimulated by C5a in a PTX-insensitive manner. Collectively, these results highlight the important regulatory roles of the Ras/Raf/MEK/ERK and c-Src/JAK pathways on the stimulation of STAT3 by activated Gα16. Demonstration of the involvement of different kinases in Gα16QL-induced STAT3 activation supports the involvement of multiple signaling pathways in the regulation of transcription by G proteins.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M307299200</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>The Journal of biological chemistry, 2003-12, Vol.278 (52), p.52154-52165</ispartof><rights>2003 © 2003 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3070-4415c8a3444566eb09c375ca5406448ee225299a4ab01ab9bb215abcfdd2ed563</citedby><cites>FETCH-LOGICAL-c3070-4415c8a3444566eb09c375ca5406448ee225299a4ab01ab9bb215abcfdd2ed563</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></links><search><creatorcontrib>Lo, Rico K.H.</creatorcontrib><creatorcontrib>Cheung, Helen</creatorcontrib><creatorcontrib>Wong, Yung H.</creatorcontrib><title>Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism</title><title>The Journal of biological chemistry</title><description>The hematopoietic-specific Gα16 protein has recently been shown to mediate receptor-induced activation of the signal transducer and activator of transcription 3 (STAT3). In the present study, we have delineated the mechanism by which Gα16 stimulates STAT3 in human embryonic kidney 293 cells. A constitutively active Gα16 mutant, Gα16QL, stimulated STAT3-dependent luciferase activity as well as the phosphorylation of STAT3 at both Tyr705 and Ser727. Gα16QL-induced STAT3 activation was enhanced by overexpression of extracellular signal-regulated kinase 1 (ERK1), but was inhibited by U0126, a Raf-1 inhibitor, and coexpression of the dominant negative mutants of Ras and Rac1. Inhibition of phospholipase Cβ, protein kinase C, and calmodulin-dependent kinase II by their respective inhibitors also suppressed Gα16QL-induced STAT3 activation. The involvement of tyrosine kinases such as c-Src and Janus kinase 2 and 3 (JAK2 and JAK3) in Gα16QL-induced activation of STAT3 was illustrated by the combined use of selective inhibitors and dominant negative mutants. In contrast, c-Jun N-terminal kinase, p38 MAPK, RhoA, Cdc42, phosphatidylinositol 3-kinase, and the epidermal growth factor receptor did not appear to be required. Similar observations were obtained with human erythroleukemia cells, where STAT3 phosphorylation was stimulated by C5a in a PTX-insensitive manner. Collectively, these results highlight the important regulatory roles of the Ras/Raf/MEK/ERK and c-Src/JAK pathways on the stimulation of STAT3 by activated Gα16. Demonstration of the involvement of different kinases in Gα16QL-induced STAT3 activation supports the involvement of multiple signaling pathways in the regulation of transcription by G proteins.</description><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNp1kMtOAjEUhhujiYhuXfcFCr0OM8sJQVQgJoKJrppeDrEEBtIWEh7LF_GZHIKJK8_mnM335z8fQveM9hgdyP7Kut5M0AGvKk7pBeowWgoiFHu_RB1KOSMVV-U1uklpRduRFeugj-G2STnkfQ4HWB9x7U4HHn9_sQLPc9js1yZDwvNFvRD4EAw22JF5dP3nekKwaTwevU6Ihx00HpqMZ-A-TRPS5hZdLc06wd3v7qK3h9Fi-EimL-OnYT0lru1KiZRMudIIKaUqCrC0cmKgnFGSFlKWAJyr9iMjjaXM2MpazpSxbuk9B68K0UW9c66L25QiLPUuho2JR82oPonRrRj9J6YFyjMAbatDgKiTC9A48CGCy9pvw3_oD34eaEE</recordid><startdate>20031226</startdate><enddate>20031226</enddate><creator>Lo, Rico K.H.</creator><creator>Cheung, Helen</creator><creator>Wong, Yung H.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20031226</creationdate><title>Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism</title><author>Lo, Rico K.H. ; Cheung, Helen ; Wong, Yung H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3070-4415c8a3444566eb09c375ca5406448ee225299a4ab01ab9bb215abcfdd2ed563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lo, Rico K.H.</creatorcontrib><creatorcontrib>Cheung, Helen</creatorcontrib><creatorcontrib>Wong, Yung H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lo, Rico K.H.</au><au>Cheung, Helen</au><au>Wong, Yung H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism</atitle><jtitle>The Journal of biological chemistry</jtitle><date>2003-12-26</date><risdate>2003</risdate><volume>278</volume><issue>52</issue><spage>52154</spage><epage>52165</epage><pages>52154-52165</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The hematopoietic-specific Gα16 protein has recently been shown to mediate receptor-induced activation of the signal transducer and activator of transcription 3 (STAT3). In the present study, we have delineated the mechanism by which Gα16 stimulates STAT3 in human embryonic kidney 293 cells. A constitutively active Gα16 mutant, Gα16QL, stimulated STAT3-dependent luciferase activity as well as the phosphorylation of STAT3 at both Tyr705 and Ser727. Gα16QL-induced STAT3 activation was enhanced by overexpression of extracellular signal-regulated kinase 1 (ERK1), but was inhibited by U0126, a Raf-1 inhibitor, and coexpression of the dominant negative mutants of Ras and Rac1. Inhibition of phospholipase Cβ, protein kinase C, and calmodulin-dependent kinase II by their respective inhibitors also suppressed Gα16QL-induced STAT3 activation. The involvement of tyrosine kinases such as c-Src and Janus kinase 2 and 3 (JAK2 and JAK3) in Gα16QL-induced activation of STAT3 was illustrated by the combined use of selective inhibitors and dominant negative mutants. In contrast, c-Jun N-terminal kinase, p38 MAPK, RhoA, Cdc42, phosphatidylinositol 3-kinase, and the epidermal growth factor receptor did not appear to be required. Similar observations were obtained with human erythroleukemia cells, where STAT3 phosphorylation was stimulated by C5a in a PTX-insensitive manner. Collectively, these results highlight the important regulatory roles of the Ras/Raf/MEK/ERK and c-Src/JAK pathways on the stimulation of STAT3 by activated Gα16. Demonstration of the involvement of different kinases in Gα16QL-induced STAT3 activation supports the involvement of multiple signaling pathways in the regulation of transcription by G proteins.</abstract><pub>Elsevier Inc</pub><doi>10.1074/jbc.M307299200</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0021-9258 |
ispartof | The Journal of biological chemistry, 2003-12, Vol.278 (52), p.52154-52165 |
issn | 0021-9258 1083-351X |
language | eng |
recordid | cdi_crossref_primary_10_1074_jbc_M307299200 |
source | EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
title | Constitutively Active Gα16 Stimulates STAT3 via a c-Src/JAK- and ERK-dependent Mechanism |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T05%3A59%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Constitutively%20Active%20G%CE%B116%20Stimulates%20STAT3%20via%20a%20c-Src/JAK-%20and%20ERK-dependent%20Mechanism&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Lo,%20Rico%20K.H.&rft.date=2003-12-26&rft.volume=278&rft.issue=52&rft.spage=52154&rft.epage=52165&rft.pages=52154-52165&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M307299200&rft_dat=%3Celsevier_cross%3ES0021925820752178%3C/elsevier_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rft_els_id=S0021925820752178&rfr_iscdi=true |