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Identification of Arrestin-3-specific Residues Necessary for JNK3 Kinase Activation
Arrestins bind active phosphorylated G protein-coupled receptors, blocking G protein activation and channeling the signaling to G protein-independent pathways. Free arrestin-3 and receptor-bound arrestin-3 scaffold the ASK1-MKK4-JNK3 module, promoting JNK3 phosphorylation, whereas highly homologous...
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| Published in: | The Journal of biological chemistry 2011-08, Vol.286 (32), p.27894-27901 |
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| Main Authors: | , , , |
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| container_end_page | 27901 |
| container_issue | 32 |
| container_start_page | 27894 |
| container_title | The Journal of biological chemistry |
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| creator | Seo, Jungwon Tsakem, Elviche L. Breitman, Maya Gurevich, Vsevolod V. |
| description | Arrestins bind active phosphorylated G protein-coupled receptors, blocking G protein activation and channeling the signaling to G protein-independent pathways. Free arrestin-3 and receptor-bound arrestin-3 scaffold the ASK1-MKK4-JNK3 module, promoting JNK3 phosphorylation, whereas highly homologous arrestin-2 does not. Here, we used arrestin-2/3 chimeras and mutants to identify key residues of arrestin-3 responsible for its ability to facilitate JNK3 activation. Our data demonstrate that both arrestin domains are involved in JNK3 activation, with the C-terminal domain being more important than the N-terminal domain. We found that Val-343 is the key contributor to this function, whereas Leu-278, Ser-280, His-350, Asp-351, His-352, and Ile-353 play supporting roles. We also show that the arrestin-3-specific difference in the arrangement of the β-strands in the C-terminal domain that underlies its lower selectivity for active phosphoreceptors does not play an appreciable role in its ability to enhance JNK3 activation. Importantly, the strength of the binding of ASK1 or JNK3, as revealed by the efficiency of co-immunoprecipitation, does not correlate with the ability of arrestin proteins to promote ASK1-dependent JNK3 phosphorylation. Thus, multiple residues on the non-receptor-binding side of arrestin-3 are crucial for JNK3 activation, and this function and the receptor-binding characteristics of arrestin can be manipulated independently by targeted mutagenesis. |
| doi_str_mv | 10.1074/jbc.M111.260448 |
| format | article |
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Free arrestin-3 and receptor-bound arrestin-3 scaffold the ASK1-MKK4-JNK3 module, promoting JNK3 phosphorylation, whereas highly homologous arrestin-2 does not. Here, we used arrestin-2/3 chimeras and mutants to identify key residues of arrestin-3 responsible for its ability to facilitate JNK3 activation. Our data demonstrate that both arrestin domains are involved in JNK3 activation, with the C-terminal domain being more important than the N-terminal domain. We found that Val-343 is the key contributor to this function, whereas Leu-278, Ser-280, His-350, Asp-351, His-352, and Ile-353 play supporting roles. We also show that the arrestin-3-specific difference in the arrangement of the β-strands in the C-terminal domain that underlies its lower selectivity for active phosphoreceptors does not play an appreciable role in its ability to enhance JNK3 activation. Importantly, the strength of the binding of ASK1 or JNK3, as revealed by the efficiency of co-immunoprecipitation, does not correlate with the ability of arrestin proteins to promote ASK1-dependent JNK3 phosphorylation. Thus, multiple residues on the non-receptor-binding side of arrestin-3 are crucial for JNK3 activation, and this function and the receptor-binding characteristics of arrestin can be manipulated independently by targeted mutagenesis.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M111.260448</identifier><identifier>PMID: 21715332</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Arrestin ; Arrestins - genetics ; Arrestins - metabolism ; Cattle ; Chlorocebus aethiops ; COS Cells ; Enzyme Activation - physiology ; G Protein-coupled Receptors (GPCRs) ; Jun N-terminal kinase (JNK) ; MAP Kinase Kinase Kinase 5 - genetics ; MAP Kinase Kinase Kinase 5 - metabolism ; MAP Kinases (MAPKs) ; Mitogen-Activated Protein Kinase 10 - genetics ; Mitogen-Activated Protein Kinase 10 - metabolism ; Phosphorylation - physiology ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Protein Interactions ; Signal Transduction ; Site-directed Mutagenesis</subject><ispartof>The Journal of biological chemistry, 2011-08, Vol.286 (32), p.27894-27901</ispartof><rights>2011 © 2011 ASBMB. 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Free arrestin-3 and receptor-bound arrestin-3 scaffold the ASK1-MKK4-JNK3 module, promoting JNK3 phosphorylation, whereas highly homologous arrestin-2 does not. Here, we used arrestin-2/3 chimeras and mutants to identify key residues of arrestin-3 responsible for its ability to facilitate JNK3 activation. Our data demonstrate that both arrestin domains are involved in JNK3 activation, with the C-terminal domain being more important than the N-terminal domain. We found that Val-343 is the key contributor to this function, whereas Leu-278, Ser-280, His-350, Asp-351, His-352, and Ile-353 play supporting roles. We also show that the arrestin-3-specific difference in the arrangement of the β-strands in the C-terminal domain that underlies its lower selectivity for active phosphoreceptors does not play an appreciable role in its ability to enhance JNK3 activation. Importantly, the strength of the binding of ASK1 or JNK3, as revealed by the efficiency of co-immunoprecipitation, does not correlate with the ability of arrestin proteins to promote ASK1-dependent JNK3 phosphorylation. Thus, multiple residues on the non-receptor-binding side of arrestin-3 are crucial for JNK3 activation, and this function and the receptor-binding characteristics of arrestin can be manipulated independently by targeted mutagenesis.</description><subject>Animals</subject><subject>Arrestin</subject><subject>Arrestins - genetics</subject><subject>Arrestins - metabolism</subject><subject>Cattle</subject><subject>Chlorocebus aethiops</subject><subject>COS Cells</subject><subject>Enzyme Activation - physiology</subject><subject>G Protein-coupled Receptors (GPCRs)</subject><subject>Jun N-terminal kinase (JNK)</subject><subject>MAP Kinase Kinase Kinase 5 - genetics</subject><subject>MAP Kinase Kinase Kinase 5 - metabolism</subject><subject>MAP Kinases (MAPKs)</subject><subject>Mitogen-Activated Protein Kinase 10 - genetics</subject><subject>Mitogen-Activated Protein Kinase 10 - metabolism</subject><subject>Phosphorylation - physiology</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Protein-Protein Interactions</subject><subject>Signal Transduction</subject><subject>Site-directed Mutagenesis</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp1kE1PwzAMhiMEYmNw5ob6B7rFSUPbC9KE-BgbQ4IduEWp60CmrZ2SbhL_no7BBAd8ycGvH8cPY-fA-8DTZDAvsP8IAH1xyZMkO2Bd4JmMpYLXQ9blXECcC5V12EkIc95WksMx6whIQUkpuuxlVFLVOOvQNK6uotpGQ-8pNK6KZRxWhNte9EzBlWsK0ZSQQjD-I7K1jx6mYxmNXWUCRUNs3OYLcsqOrFkEOvt-e2x2ezO7vo8nT3ej6-EkRsWzJjbW8oLnmENWJJCj5YJEwoVEqfJMJSVmZLkiC5TIAjMUZUogTIqAxqSyx6522NW6WFKJ7R3eLPTKu2X7P10bp_92Kveu3-qNlqCAS9UCBjsA-joET3Y_C1xv9epWr97q1Tu97cTF75X7_I_PNpDvAtTevXHkdUBHFVLpPGGjy9r9C_8E3YKLWA</recordid><startdate>20110812</startdate><enddate>20110812</enddate><creator>Seo, Jungwon</creator><creator>Tsakem, Elviche L.</creator><creator>Breitman, Maya</creator><creator>Gurevich, Vsevolod V.</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>5PM</scope></search><sort><creationdate>20110812</creationdate><title>Identification of Arrestin-3-specific Residues Necessary for JNK3 Kinase Activation</title><author>Seo, Jungwon ; Tsakem, Elviche L. ; Breitman, Maya ; Gurevich, Vsevolod V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-aff0b09c918b419cf02e24023c359854dc8ef05ef1e43bc8c2d7e12a7c1caa73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Arrestin</topic><topic>Arrestins - genetics</topic><topic>Arrestins - metabolism</topic><topic>Cattle</topic><topic>Chlorocebus aethiops</topic><topic>COS Cells</topic><topic>Enzyme Activation - physiology</topic><topic>G Protein-coupled Receptors (GPCRs)</topic><topic>Jun N-terminal kinase (JNK)</topic><topic>MAP Kinase Kinase Kinase 5 - genetics</topic><topic>MAP Kinase Kinase Kinase 5 - metabolism</topic><topic>MAP Kinases (MAPKs)</topic><topic>Mitogen-Activated Protein Kinase 10 - genetics</topic><topic>Mitogen-Activated Protein Kinase 10 - metabolism</topic><topic>Phosphorylation - physiology</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>Protein-Protein Interactions</topic><topic>Signal Transduction</topic><topic>Site-directed Mutagenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seo, Jungwon</creatorcontrib><creatorcontrib>Tsakem, Elviche L.</creatorcontrib><creatorcontrib>Breitman, Maya</creatorcontrib><creatorcontrib>Gurevich, Vsevolod V.</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>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seo, Jungwon</au><au>Tsakem, Elviche L.</au><au>Breitman, Maya</au><au>Gurevich, Vsevolod V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Arrestin-3-specific Residues Necessary for JNK3 Kinase Activation</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2011-08-12</date><risdate>2011</risdate><volume>286</volume><issue>32</issue><spage>27894</spage><epage>27901</epage><pages>27894-27901</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Arrestins bind active phosphorylated G protein-coupled receptors, blocking G protein activation and channeling the signaling to G protein-independent pathways. 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Importantly, the strength of the binding of ASK1 or JNK3, as revealed by the efficiency of co-immunoprecipitation, does not correlate with the ability of arrestin proteins to promote ASK1-dependent JNK3 phosphorylation. Thus, multiple residues on the non-receptor-binding side of arrestin-3 are crucial for JNK3 activation, and this function and the receptor-binding characteristics of arrestin can be manipulated independently by targeted mutagenesis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21715332</pmid><doi>10.1074/jbc.M111.260448</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | ScienceDirect (Online service); PubMed Central |
| subjects | Animals Arrestin Arrestins - genetics Arrestins - metabolism Cattle Chlorocebus aethiops COS Cells Enzyme Activation - physiology G Protein-coupled Receptors (GPCRs) Jun N-terminal kinase (JNK) MAP Kinase Kinase Kinase 5 - genetics MAP Kinase Kinase Kinase 5 - metabolism MAP Kinases (MAPKs) Mitogen-Activated Protein Kinase 10 - genetics Mitogen-Activated Protein Kinase 10 - metabolism Phosphorylation - physiology Protein Structure, Secondary Protein Structure, Tertiary Protein-Protein Interactions Signal Transduction Site-directed Mutagenesis |
| title | Identification of Arrestin-3-specific Residues Necessary for JNK3 Kinase Activation |
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