Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription
SMAD and JNK cascades are essential components of the transforming growth factor-beta (TGF-beta) signaling machinery and are implicated in common transcriptional responses. However, the relationship of these pathways to one another downstream of the TGF-beta receptor complex is unknown. We show that...
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Veröffentlicht in: | The Journal of biological chemistry 1999-12, Vol.274 (52), p.37413-37420 |
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creator | Engel, M E McDonnell, M A Law, B K Moses, H L |
description | SMAD and JNK cascades are essential components of the transforming growth factor-beta (TGF-beta) signaling machinery and are implicated in common transcriptional responses. However, the relationship of these pathways to one another downstream of the TGF-beta receptor complex is unknown. We show that JNK is rapidly activated by TGF-beta in a SMAD-independent manner and phosphorylates Smad3 outside its -SSXS motif. Smad3 phosphorylation by JNK facilitates both its activation by the TGF-beta receptor complex and its nuclear accumulation. JNK regulates SMAD- and TGF-beta-mediated transcriptional responses, yet JNK activators only partially stimulate transcriptional responses characteristic of TGF-beta without coincident SMAD pathway activation. These results suggest an interdependent relationship between the JNK and SMAD pathways in TGF-beta-mediated transcription. |
doi_str_mv | 10.1074/jbc.274.52.37413 |
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These results suggest an interdependent relationship between the JNK and SMAD pathways in TGF-beta-mediated transcription.</description><identifier>ISSN: 0021-9258</identifier><identifier>DOI: 10.1074/jbc.274.52.37413</identifier><identifier>PMID: 10601313</identifier><language>eng</language><publisher>United States</publisher><subject>Cells, Cultured ; DNA-Binding Proteins - physiology ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Kinase 4 ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinase Kinases - physiology ; Mitogen-Activated Protein Kinases - physiology ; Phosphorylation ; Plasminogen Activator Inhibitor 1 - biosynthesis ; rhoA GTP-Binding Protein - physiology ; Smad2 Protein ; Smad3 Protein ; Trans-Activators - physiology ; Transcription, Genetic - drug effects ; Transforming Growth Factor beta - pharmacology ; transforming growth factor-b</subject><ispartof>The Journal of biological chemistry, 1999-12, Vol.274 (52), p.37413-37420</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-2a8ca0b019db2140c5e301eb6d7249aab3ca795454827ff8f340fde0e03312183</citedby><cites>FETCH-LOGICAL-c415t-2a8ca0b019db2140c5e301eb6d7249aab3ca795454827ff8f340fde0e03312183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10601313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Engel, M E</creatorcontrib><creatorcontrib>McDonnell, M A</creatorcontrib><creatorcontrib>Law, B K</creatorcontrib><creatorcontrib>Moses, H L</creatorcontrib><title>Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>SMAD and JNK cascades are essential components of the transforming growth factor-beta (TGF-beta) signaling machinery and are implicated in common transcriptional responses. However, the relationship of these pathways to one another downstream of the TGF-beta receptor complex is unknown. We show that JNK is rapidly activated by TGF-beta in a SMAD-independent manner and phosphorylates Smad3 outside its -SSXS motif. Smad3 phosphorylation by JNK facilitates both its activation by the TGF-beta receptor complex and its nuclear accumulation. JNK regulates SMAD- and TGF-beta-mediated transcriptional responses, yet JNK activators only partially stimulate transcriptional responses characteristic of TGF-beta without coincident SMAD pathway activation. These results suggest an interdependent relationship between the JNK and SMAD pathways in TGF-beta-mediated transcription.</description><subject>Cells, Cultured</subject><subject>DNA-Binding Proteins - physiology</subject><subject>JNK Mitogen-Activated Protein Kinases</subject><subject>MAP Kinase Kinase 4</subject><subject>Mitogen-Activated Protein Kinase 3</subject><subject>Mitogen-Activated Protein Kinase Kinases - physiology</subject><subject>Mitogen-Activated Protein Kinases - physiology</subject><subject>Phosphorylation</subject><subject>Plasminogen Activator Inhibitor 1 - biosynthesis</subject><subject>rhoA GTP-Binding Protein - physiology</subject><subject>Smad2 Protein</subject><subject>Smad3 Protein</subject><subject>Trans-Activators - physiology</subject><subject>Transcription, Genetic - drug effects</subject><subject>Transforming Growth Factor beta - pharmacology</subject><subject>transforming growth factor-b</subject><issn>0021-9258</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkD1PwzAQhj2AaCnsTCgTW8L5I3UyVuWrUGAAZsuxneIqcYLtCvHvSUkHbjmd9LyvdA9CFxgyDJxdbyuVEc6ynGSUM0yP0BSA4LQkeTFBpyFsYRhW4hM0wTAHTDGdIrFy0XhteuO0cTF5e17cJNLp5PHlKQl242Rj3SaxLoleulB3vt3fG999x8-klip2Pq1MlGlrtJXR6BFU3vbRdu4MHdeyCeb8sGfo4-72ffmQrl_vV8vFOlUM5zElslASKsClrghmoHJDAZtqrjlhpZQVVZKXOctZQXhdFzVlUGsDBijFBBd0hq7G3t53XzsTomhtUKZppDPdLgjM2TznQAYQRlD5LgRvatF720r_IzCIvUgxiBSDSJET8SdyiFweunfV8OW_wGiR_gLL0nF1</recordid><startdate>19991224</startdate><enddate>19991224</enddate><creator>Engel, M E</creator><creator>McDonnell, M A</creator><creator>Law, B K</creator><creator>Moses, H L</creator><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>7TM</scope></search><sort><creationdate>19991224</creationdate><title>Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription</title><author>Engel, M E ; McDonnell, M A ; Law, B K ; Moses, H L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-2a8ca0b019db2140c5e301eb6d7249aab3ca795454827ff8f340fde0e03312183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Cells, Cultured</topic><topic>DNA-Binding Proteins - physiology</topic><topic>JNK Mitogen-Activated Protein Kinases</topic><topic>MAP Kinase Kinase 4</topic><topic>Mitogen-Activated Protein Kinase 3</topic><topic>Mitogen-Activated Protein Kinase Kinases - physiology</topic><topic>Mitogen-Activated Protein Kinases - physiology</topic><topic>Phosphorylation</topic><topic>Plasminogen Activator Inhibitor 1 - biosynthesis</topic><topic>rhoA GTP-Binding Protein - physiology</topic><topic>Smad2 Protein</topic><topic>Smad3 Protein</topic><topic>Trans-Activators - physiology</topic><topic>Transcription, Genetic - drug effects</topic><topic>Transforming Growth Factor beta - pharmacology</topic><topic>transforming growth factor-b</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Engel, M E</creatorcontrib><creatorcontrib>McDonnell, M A</creatorcontrib><creatorcontrib>Law, B K</creatorcontrib><creatorcontrib>Moses, H L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Engel, M E</au><au>McDonnell, M A</au><au>Law, B K</au><au>Moses, H L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1999-12-24</date><risdate>1999</risdate><volume>274</volume><issue>52</issue><spage>37413</spage><epage>37420</epage><pages>37413-37420</pages><issn>0021-9258</issn><abstract>SMAD and JNK cascades are essential components of the transforming growth factor-beta (TGF-beta) signaling machinery and are implicated in common transcriptional responses. 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subjects | Cells, Cultured DNA-Binding Proteins - physiology JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase Kinases - physiology Mitogen-Activated Protein Kinases - physiology Phosphorylation Plasminogen Activator Inhibitor 1 - biosynthesis rhoA GTP-Binding Protein - physiology Smad2 Protein Smad3 Protein Trans-Activators - physiology Transcription, Genetic - drug effects Transforming Growth Factor beta - pharmacology transforming growth factor-b |
title | Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription |
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