Suppression of Androgen Receptor Transactivation by Pyk2 via Interaction and Phosphorylation of the ARA55 Coregulator
The proline-rich tyrosine kinase 2 (Pyk2) was first identified as a key kinase linked to the MAP kinase and JNK signaling pathways that play important roles in cell growth and adhesion. The linkage between Pyk2 and the androgen receptor (AR), an important transcription factor in prostate cancer prog...
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| Veröffentlicht in: | The Journal of biological chemistry 2002-05, Vol.277 (18), p.15426-15431 |
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| container_title | The Journal of biological chemistry |
| container_volume | 277 |
| creator | Wang, Xin Yang, Yue Guo, Xiaojian Sampson, Erik R. Hsu, Cheng-Lung Tsai, Meng-Yin Yeh, Shuyuan Wu, Guan Guo, Yinglu Chang, Chawnshang |
| description | The proline-rich tyrosine kinase 2 (Pyk2) was first identified as a key kinase linked to the MAP kinase and JNK signaling pathways that play important roles in cell growth and adhesion. The linkage between Pyk2 and the androgen receptor (AR), an important transcription factor in prostate cancer progression, however, remains unclear. Here we report that using the full-length androgen receptor-associated protein, ARA55, coregulator as bait, we were able to isolate an ARA55-interacting protein, Pyk2, and demonstrated that Pyk2 could repress AR transactivation via inactivation of ARA55. This inactivation may result from the direct phosphorylation of ARA55 by Pyk2 at tyrosine 43, impairing the coactivator activity of ARA55 and/or sequestering ARA55 to reduce its interaction with AR. Our finding that Pyk2 can indirectly modulate AR function via interaction and/or phosphorylation of ARA55 not only expands the role of Pyk2 in AR-mediated prostate cancer growth but also strengthens the role of ARA55 as an AR coregulator. |
| doi_str_mv | 10.1074/jbc.M111218200 |
| format | Article |
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The linkage between Pyk2 and the androgen receptor (AR), an important transcription factor in prostate cancer progression, however, remains unclear. Here we report that using the full-length androgen receptor-associated protein, ARA55, coregulator as bait, we were able to isolate an ARA55-interacting protein, Pyk2, and demonstrated that Pyk2 could repress AR transactivation via inactivation of ARA55. This inactivation may result from the direct phosphorylation of ARA55 by Pyk2 at tyrosine 43, impairing the coactivator activity of ARA55 and/or sequestering ARA55 to reduce its interaction with AR. Our finding that Pyk2 can indirectly modulate AR function via interaction and/or phosphorylation of ARA55 not only expands the role of Pyk2 in AR-mediated prostate cancer growth but also strengthens the role of ARA55 as an AR coregulator.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M111218200</identifier><identifier>PMID: 11856738</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; ARA55 protein ; Cell Line ; Chlorocebus aethiops ; COS Cells ; Focal Adhesion Kinase 2 ; Gene Library ; Genes, Reporter ; Humans ; Intracellular Signaling Peptides and Proteins ; LIM Domain Proteins ; Male ; Mutagenesis, Site-Directed ; Phosphorylation ; Prostate - metabolism ; Protein-Tyrosine Kinases - metabolism ; Pyk2 protein ; Receptors, Androgen - genetics ; Recombinant Fusion Proteins - metabolism ; Saccharomyces cerevisiae - genetics ; Trans-Activators - metabolism ; Transcriptional Activation ; Transfection</subject><ispartof>The Journal of biological chemistry, 2002-05, Vol.277 (18), p.15426-15431</ispartof><rights>2002 © 2002 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-c440t-679ffb25dc9c4945d0e8b12feebb1a54b367588453a8af3cfe3d81c31dbdf8223</citedby><cites>FETCH-LOGICAL-c440t-679ffb25dc9c4945d0e8b12feebb1a54b367588453a8af3cfe3d81c31dbdf8223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11856738$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xin</creatorcontrib><creatorcontrib>Yang, Yue</creatorcontrib><creatorcontrib>Guo, Xiaojian</creatorcontrib><creatorcontrib>Sampson, Erik R.</creatorcontrib><creatorcontrib>Hsu, Cheng-Lung</creatorcontrib><creatorcontrib>Tsai, Meng-Yin</creatorcontrib><creatorcontrib>Yeh, Shuyuan</creatorcontrib><creatorcontrib>Wu, Guan</creatorcontrib><creatorcontrib>Guo, Yinglu</creatorcontrib><creatorcontrib>Chang, Chawnshang</creatorcontrib><title>Suppression of Androgen Receptor Transactivation by Pyk2 via Interaction and Phosphorylation of the ARA55 Coregulator</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The proline-rich tyrosine kinase 2 (Pyk2) was first identified as a key kinase linked to the MAP kinase and JNK signaling pathways that play important roles in cell growth and adhesion. The linkage between Pyk2 and the androgen receptor (AR), an important transcription factor in prostate cancer progression, however, remains unclear. Here we report that using the full-length androgen receptor-associated protein, ARA55, coregulator as bait, we were able to isolate an ARA55-interacting protein, Pyk2, and demonstrated that Pyk2 could repress AR transactivation via inactivation of ARA55. This inactivation may result from the direct phosphorylation of ARA55 by Pyk2 at tyrosine 43, impairing the coactivator activity of ARA55 and/or sequestering ARA55 to reduce its interaction with AR. Our finding that Pyk2 can indirectly modulate AR function via interaction and/or phosphorylation of ARA55 not only expands the role of Pyk2 in AR-mediated prostate cancer growth but also strengthens the role of ARA55 as an AR coregulator.</description><subject>Animals</subject><subject>ARA55 protein</subject><subject>Cell Line</subject><subject>Chlorocebus aethiops</subject><subject>COS Cells</subject><subject>Focal Adhesion Kinase 2</subject><subject>Gene Library</subject><subject>Genes, Reporter</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>LIM Domain Proteins</subject><subject>Male</subject><subject>Mutagenesis, Site-Directed</subject><subject>Phosphorylation</subject><subject>Prostate - metabolism</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Pyk2 protein</subject><subject>Receptors, Androgen - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transcriptional Activation</subject><subject>Transfection</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE2P0zAQhi0EYsvClSPyAXFL8dhx4x6rio-VFrFaFomb5Y9J46WNg50U9d_jKpX2hC8jeZ55Z_QQ8hbYElhTf3y0bvkNADgoztgzsgCmRCUk_HpOFoxxqNZcqivyKudHVl69hpfkCkDJVSPUgkw_pmFImHOIPY0t3fQ-xR329B4dDmNM9CGZPhs3hqMZz5A90bvTb06PwdCbfsR07pV_03t618U8dDGd9jNbAscO6eZ-IyXdxoS7qXRiek1etGaf8c2lXpOfnz89bL9Wt9-_3Gw3t5WrazZWq2bdtpZL79auXtfSM1QWeItoLRhZW7FqpFK1FEaZVrgWhVfgBHjrW8W5uCYf5twhxT8T5lEfQna435se45Q1KFFUsKaAyxl0KeacsNVDCgeTThqYPovWRbR-El0G3l2SJ3tA_4RfzBbg_Qx0Ydf9DQm1DdF1eNC8acpiDbLmq4KpGcOi4Rgw6ewC9g59GXGj9jH874R_AH6ZtA</recordid><startdate>20020503</startdate><enddate>20020503</enddate><creator>Wang, Xin</creator><creator>Yang, Yue</creator><creator>Guo, Xiaojian</creator><creator>Sampson, Erik R.</creator><creator>Hsu, Cheng-Lung</creator><creator>Tsai, Meng-Yin</creator><creator>Yeh, Shuyuan</creator><creator>Wu, Guan</creator><creator>Guo, Yinglu</creator><creator>Chang, Chawnshang</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>7TM</scope></search><sort><creationdate>20020503</creationdate><title>Suppression of Androgen Receptor Transactivation by Pyk2 via Interaction and Phosphorylation of the ARA55 Coregulator</title><author>Wang, Xin ; Yang, Yue ; Guo, Xiaojian ; Sampson, Erik R. ; Hsu, Cheng-Lung ; Tsai, Meng-Yin ; Yeh, Shuyuan ; Wu, Guan ; Guo, Yinglu ; Chang, Chawnshang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-679ffb25dc9c4945d0e8b12feebb1a54b367588453a8af3cfe3d81c31dbdf8223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>ARA55 protein</topic><topic>Cell Line</topic><topic>Chlorocebus aethiops</topic><topic>COS Cells</topic><topic>Focal Adhesion Kinase 2</topic><topic>Gene Library</topic><topic>Genes, Reporter</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>LIM Domain Proteins</topic><topic>Male</topic><topic>Mutagenesis, Site-Directed</topic><topic>Phosphorylation</topic><topic>Prostate - metabolism</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Pyk2 protein</topic><topic>Receptors, Androgen - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Trans-Activators - metabolism</topic><topic>Transcriptional Activation</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xin</creatorcontrib><creatorcontrib>Yang, Yue</creatorcontrib><creatorcontrib>Guo, Xiaojian</creatorcontrib><creatorcontrib>Sampson, Erik R.</creatorcontrib><creatorcontrib>Hsu, Cheng-Lung</creatorcontrib><creatorcontrib>Tsai, Meng-Yin</creatorcontrib><creatorcontrib>Yeh, Shuyuan</creatorcontrib><creatorcontrib>Wu, Guan</creatorcontrib><creatorcontrib>Guo, Yinglu</creatorcontrib><creatorcontrib>Chang, Chawnshang</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Wang, Xin</au><au>Yang, Yue</au><au>Guo, Xiaojian</au><au>Sampson, Erik R.</au><au>Hsu, Cheng-Lung</au><au>Tsai, Meng-Yin</au><au>Yeh, Shuyuan</au><au>Wu, Guan</au><au>Guo, Yinglu</au><au>Chang, Chawnshang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppression of Androgen Receptor Transactivation by Pyk2 via Interaction and Phosphorylation of the ARA55 Coregulator</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2002-05-03</date><risdate>2002</risdate><volume>277</volume><issue>18</issue><spage>15426</spage><epage>15431</epage><pages>15426-15431</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The proline-rich tyrosine kinase 2 (Pyk2) was first identified as a key kinase linked to the MAP kinase and JNK signaling pathways that play important roles in cell growth and adhesion. The linkage between Pyk2 and the androgen receptor (AR), an important transcription factor in prostate cancer progression, however, remains unclear. Here we report that using the full-length androgen receptor-associated protein, ARA55, coregulator as bait, we were able to isolate an ARA55-interacting protein, Pyk2, and demonstrated that Pyk2 could repress AR transactivation via inactivation of ARA55. This inactivation may result from the direct phosphorylation of ARA55 by Pyk2 at tyrosine 43, impairing the coactivator activity of ARA55 and/or sequestering ARA55 to reduce its interaction with AR. 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| subjects | Animals ARA55 protein Cell Line Chlorocebus aethiops COS Cells Focal Adhesion Kinase 2 Gene Library Genes, Reporter Humans Intracellular Signaling Peptides and Proteins LIM Domain Proteins Male Mutagenesis, Site-Directed Phosphorylation Prostate - metabolism Protein-Tyrosine Kinases - metabolism Pyk2 protein Receptors, Androgen - genetics Recombinant Fusion Proteins - metabolism Saccharomyces cerevisiae - genetics Trans-Activators - metabolism Transcriptional Activation Transfection |
| title | Suppression of Androgen Receptor Transactivation by Pyk2 via Interaction and Phosphorylation of the ARA55 Coregulator |
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