PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors
Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they hav...
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| Veröffentlicht in: | The Journal of biological chemistry 2012-06, Vol.287 (25), p.21012-21024 |
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| creator | Kim, Jung Kuk Kwon, Ohman Kim, Jinho Kim, Eung-Kyun Park, Hye Kyung Lee, Ji Eun Kim, Kyung Lock Choi, Jung Woong Lim, Seyoung Seok, Heon Lee-Kwon, Whaseon Choi, Jang Hyun Kang, Byoung Heon Kim, Sanguk Ryu, Sung Ho Suh, Pann-Ghill |
| description | Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they have the potential to interact with different PDZ proteins. In this study, we identified PDZ domain-containing 1 (PDZK1) as a PDZ protein that specifically interacts with PLC-β3. To elucidate the functional roles of PDZK1, we next screened for potential interacting proteins of PDZK1 and identified the somatostatin receptors (SSTRs) as another protein that interacts with PDZK1. Through these interactions, PDZK1 assembles as a ternary complex with PLC-β3 and SSTRs. Interestingly, the expression of PDZK1 and PLC-β3, but not PLC-β1, markedly potentiated SST-induced PLC activation. However, disruption of the ternary complex inhibited SST-induced PLC activation, which suggests that PDZK1-mediated complex formation is required for the specific activation of PLC-β3 by SST. Consistent with this observation, the knockdown of PDZK1 or PLC-β3, but not that of PLC-β1, significantly inhibited SST-induced intracellular Ca2+ mobilization, which further attenuated subsequent ERK1/2 phosphorylation. Taken together, our results strongly suggest that the formation of a complex between SSTRs, PDZK1, and PLC-β3 is essential for the specific activation of PLC-β3 and the subsequent physiologic responses by SST.
The four PLC-β subtypes (β1–β4) have different roles in GPCR-mediated signaling despite having similar structures and regulatory modes.
PDZK1 mediates the physical coupling of PLC-β3 to SSTRs using different PDZ domains.
PLC-β3 is specifically involved in SSTR-mediated signaling via its interaction with PDZK1.
The subtype-specific role of PLC-β is mediated by differential interactions with PDZ proteins and GPCRs. |
| doi_str_mv | 10.1074/jbc.M111.337865 |
| format | Article |
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The four PLC-β subtypes (β1–β4) have different roles in GPCR-mediated signaling despite having similar structures and regulatory modes.
PDZK1 mediates the physical coupling of PLC-β3 to SSTRs using different PDZ domains.
PLC-β3 is specifically involved in SSTR-mediated signaling via its interaction with PDZK1.
The subtype-specific role of PLC-β is mediated by differential interactions with PDZ proteins and GPCRs.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M111.337865</identifier><identifier>PMID: 22528496</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Bioinformatics ; Calcium - metabolism ; Calcium Signaling ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Enzyme Activation ; G Protein-coupled Receptors (GPCR) ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Membrane Proteins ; Mitogen-Activated Protein Kinase 1 - genetics ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - genetics ; Mitogen-Activated Protein Kinase 3 - metabolism ; Multiprotein Complexes - genetics ; Multiprotein Complexes - metabolism ; PDZ Protein ; PDZK1 ; Phospholipase C ; Phospholipase C beta - genetics ; Phospholipase C beta - metabolism ; Phosphorylation - physiology ; Receptors, Somatostatin - genetics ; Receptors, Somatostatin - metabolism ; Scaffold Proteins ; Signal Transduction ; Somatostatin ; Somatostatin - genetics ; Somatostatin - metabolism</subject><ispartof>The Journal of biological chemistry, 2012-06, Vol.287 (25), p.21012-21024</ispartof><rights>2012 © 2012 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2012 by The American Society for Biochemistry and Molecular Biology, Inc. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3585-458771847fbabbcb64d204ab7815767db84691655f24d1afd9d871235a5a996f3</citedby><cites>FETCH-LOGICAL-c3585-458771847fbabbcb64d204ab7815767db84691655f24d1afd9d871235a5a996f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375525/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375525/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22528496$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jung Kuk</creatorcontrib><creatorcontrib>Kwon, Ohman</creatorcontrib><creatorcontrib>Kim, Jinho</creatorcontrib><creatorcontrib>Kim, Eung-Kyun</creatorcontrib><creatorcontrib>Park, Hye Kyung</creatorcontrib><creatorcontrib>Lee, Ji Eun</creatorcontrib><creatorcontrib>Kim, Kyung Lock</creatorcontrib><creatorcontrib>Choi, Jung Woong</creatorcontrib><creatorcontrib>Lim, Seyoung</creatorcontrib><creatorcontrib>Seok, Heon</creatorcontrib><creatorcontrib>Lee-Kwon, Whaseon</creatorcontrib><creatorcontrib>Choi, Jang Hyun</creatorcontrib><creatorcontrib>Kang, Byoung Heon</creatorcontrib><creatorcontrib>Kim, Sanguk</creatorcontrib><creatorcontrib>Ryu, Sung Ho</creatorcontrib><creatorcontrib>Suh, Pann-Ghill</creatorcontrib><title>PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they have the potential to interact with different PDZ proteins. In this study, we identified PDZ domain-containing 1 (PDZK1) as a PDZ protein that specifically interacts with PLC-β3. To elucidate the functional roles of PDZK1, we next screened for potential interacting proteins of PDZK1 and identified the somatostatin receptors (SSTRs) as another protein that interacts with PDZK1. Through these interactions, PDZK1 assembles as a ternary complex with PLC-β3 and SSTRs. Interestingly, the expression of PDZK1 and PLC-β3, but not PLC-β1, markedly potentiated SST-induced PLC activation. However, disruption of the ternary complex inhibited SST-induced PLC activation, which suggests that PDZK1-mediated complex formation is required for the specific activation of PLC-β3 by SST. Consistent with this observation, the knockdown of PDZK1 or PLC-β3, but not that of PLC-β1, significantly inhibited SST-induced intracellular Ca2+ mobilization, which further attenuated subsequent ERK1/2 phosphorylation. Taken together, our results strongly suggest that the formation of a complex between SSTRs, PDZK1, and PLC-β3 is essential for the specific activation of PLC-β3 and the subsequent physiologic responses by SST.
The four PLC-β subtypes (β1–β4) have different roles in GPCR-mediated signaling despite having similar structures and regulatory modes.
PDZK1 mediates the physical coupling of PLC-β3 to SSTRs using different PDZ domains.
PLC-β3 is specifically involved in SSTR-mediated signaling via its interaction with PDZK1.
The subtype-specific role of PLC-β is mediated by differential interactions with PDZ proteins and GPCRs.</description><subject>Bioinformatics</subject><subject>Calcium - metabolism</subject><subject>Calcium Signaling</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Enzyme Activation</subject><subject>G Protein-coupled Receptors (GPCR)</subject><subject>Gene Knockdown Techniques</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Membrane Proteins</subject><subject>Mitogen-Activated Protein Kinase 1 - genetics</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - genetics</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Multiprotein Complexes - genetics</subject><subject>Multiprotein Complexes - metabolism</subject><subject>PDZ Protein</subject><subject>PDZK1</subject><subject>Phospholipase C</subject><subject>Phospholipase C beta - genetics</subject><subject>Phospholipase C beta - metabolism</subject><subject>Phosphorylation - physiology</subject><subject>Receptors, Somatostatin - genetics</subject><subject>Receptors, Somatostatin - metabolism</subject><subject>Scaffold Proteins</subject><subject>Signal Transduction</subject><subject>Somatostatin</subject><subject>Somatostatin - genetics</subject><subject>Somatostatin - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhi1ERZfCmRvysT1kGztx7FyQqi0F1K1YlSIhLpbjTHZdJXawvQt9LU48Bc-Et7tU9IAvY3n--f-RP4RekXxKcl6e3jZ6ekUImRYFFxV7giYkF0VWMPLlKZrkOSVZTZk4RM9DuM3TKWvyDB1Syqgo62qCfi3Ov-JzNyhjM-1sTNXYJSb4ODUuyQleeBfBWHwNy3WvIgS8WLkwrlxvRhUAz7LfP4uknt9fTrIwgjad0fhMR7NR0TiLXYc_pYjoQkwPFjd3-ML5YRuk8A14q_wdnrlh7OEH_m7iCu_tsLLt49Fr0DBG58MLdNCpPsDLfT1Cny_e3szeZ_OP7z7MzuaZLphgWckE50SUvGtU0-imKlual6rhgjBe8bYRZVWTirGOli1RXVu3ghNaMMVUXVddcYTe7HzHdTNAq8FGr3o5ejOkraVTRj7uWLOSS7eRiQhjlCWD472Bd9_WEKIcTNDQ98qCWwdJEiRCq7riSXq6k2rvQvDQPcSQXG55y8RbbnnLHe808frf7R70fwEnQb0TQPqjjQEvgzZgNbTGg46ydea_5n8Ashq9Pg</recordid><startdate>20120615</startdate><enddate>20120615</enddate><creator>Kim, Jung Kuk</creator><creator>Kwon, Ohman</creator><creator>Kim, Jinho</creator><creator>Kim, Eung-Kyun</creator><creator>Park, Hye Kyung</creator><creator>Lee, Ji Eun</creator><creator>Kim, Kyung Lock</creator><creator>Choi, Jung Woong</creator><creator>Lim, Seyoung</creator><creator>Seok, Heon</creator><creator>Lee-Kwon, Whaseon</creator><creator>Choi, Jang Hyun</creator><creator>Kang, Byoung Heon</creator><creator>Kim, Sanguk</creator><creator>Ryu, Sung Ho</creator><creator>Suh, Pann-Ghill</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120615</creationdate><title>PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors</title><author>Kim, Jung Kuk ; Kwon, Ohman ; Kim, Jinho ; Kim, Eung-Kyun ; Park, Hye Kyung ; Lee, Ji Eun ; Kim, Kyung Lock ; Choi, Jung Woong ; Lim, Seyoung ; Seok, Heon ; Lee-Kwon, Whaseon ; Choi, Jang Hyun ; Kang, Byoung Heon ; Kim, Sanguk ; Ryu, Sung Ho ; Suh, Pann-Ghill</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3585-458771847fbabbcb64d204ab7815767db84691655f24d1afd9d871235a5a996f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Bioinformatics</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Enzyme Activation</topic><topic>G Protein-coupled Receptors (GPCR)</topic><topic>Gene Knockdown Techniques</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Membrane Proteins</topic><topic>Mitogen-Activated Protein Kinase 1 - genetics</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - genetics</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Multiprotein Complexes - genetics</topic><topic>Multiprotein Complexes - metabolism</topic><topic>PDZ Protein</topic><topic>PDZK1</topic><topic>Phospholipase C</topic><topic>Phospholipase C beta - genetics</topic><topic>Phospholipase C beta - metabolism</topic><topic>Phosphorylation - physiology</topic><topic>Receptors, Somatostatin - genetics</topic><topic>Receptors, Somatostatin - metabolism</topic><topic>Scaffold Proteins</topic><topic>Signal Transduction</topic><topic>Somatostatin</topic><topic>Somatostatin - genetics</topic><topic>Somatostatin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jung Kuk</creatorcontrib><creatorcontrib>Kwon, Ohman</creatorcontrib><creatorcontrib>Kim, Jinho</creatorcontrib><creatorcontrib>Kim, Eung-Kyun</creatorcontrib><creatorcontrib>Park, Hye Kyung</creatorcontrib><creatorcontrib>Lee, Ji Eun</creatorcontrib><creatorcontrib>Kim, Kyung Lock</creatorcontrib><creatorcontrib>Choi, Jung Woong</creatorcontrib><creatorcontrib>Lim, Seyoung</creatorcontrib><creatorcontrib>Seok, Heon</creatorcontrib><creatorcontrib>Lee-Kwon, Whaseon</creatorcontrib><creatorcontrib>Choi, Jang Hyun</creatorcontrib><creatorcontrib>Kang, Byoung Heon</creatorcontrib><creatorcontrib>Kim, Sanguk</creatorcontrib><creatorcontrib>Ryu, Sung Ho</creatorcontrib><creatorcontrib>Suh, Pann-Ghill</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>MEDLINE - Academic</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>Kim, Jung Kuk</au><au>Kwon, Ohman</au><au>Kim, Jinho</au><au>Kim, Eung-Kyun</au><au>Park, Hye Kyung</au><au>Lee, Ji Eun</au><au>Kim, Kyung Lock</au><au>Choi, Jung Woong</au><au>Lim, Seyoung</au><au>Seok, Heon</au><au>Lee-Kwon, Whaseon</au><au>Choi, Jang Hyun</au><au>Kang, Byoung Heon</au><au>Kim, Sanguk</au><au>Ryu, Sung Ho</au><au>Suh, Pann-Ghill</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2012-06-15</date><risdate>2012</risdate><volume>287</volume><issue>25</issue><spage>21012</spage><epage>21024</epage><pages>21012-21024</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they have the potential to interact with different PDZ proteins. In this study, we identified PDZ domain-containing 1 (PDZK1) as a PDZ protein that specifically interacts with PLC-β3. To elucidate the functional roles of PDZK1, we next screened for potential interacting proteins of PDZK1 and identified the somatostatin receptors (SSTRs) as another protein that interacts with PDZK1. Through these interactions, PDZK1 assembles as a ternary complex with PLC-β3 and SSTRs. Interestingly, the expression of PDZK1 and PLC-β3, but not PLC-β1, markedly potentiated SST-induced PLC activation. However, disruption of the ternary complex inhibited SST-induced PLC activation, which suggests that PDZK1-mediated complex formation is required for the specific activation of PLC-β3 by SST. Consistent with this observation, the knockdown of PDZK1 or PLC-β3, but not that of PLC-β1, significantly inhibited SST-induced intracellular Ca2+ mobilization, which further attenuated subsequent ERK1/2 phosphorylation. Taken together, our results strongly suggest that the formation of a complex between SSTRs, PDZK1, and PLC-β3 is essential for the specific activation of PLC-β3 and the subsequent physiologic responses by SST.
The four PLC-β subtypes (β1–β4) have different roles in GPCR-mediated signaling despite having similar structures and regulatory modes.
PDZK1 mediates the physical coupling of PLC-β3 to SSTRs using different PDZ domains.
PLC-β3 is specifically involved in SSTR-mediated signaling via its interaction with PDZK1.
The subtype-specific role of PLC-β is mediated by differential interactions with PDZ proteins and GPCRs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22528496</pmid><doi>10.1074/jbc.M111.337865</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 2012-06, Vol.287 (25), p.21012-21024 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3375525 |
| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Bioinformatics Calcium - metabolism Calcium Signaling Carrier Proteins - genetics Carrier Proteins - metabolism Enzyme Activation G Protein-coupled Receptors (GPCR) Gene Knockdown Techniques HEK293 Cells Humans Membrane Proteins Mitogen-Activated Protein Kinase 1 - genetics Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - genetics Mitogen-Activated Protein Kinase 3 - metabolism Multiprotein Complexes - genetics Multiprotein Complexes - metabolism PDZ Protein PDZK1 Phospholipase C Phospholipase C beta - genetics Phospholipase C beta - metabolism Phosphorylation - physiology Receptors, Somatostatin - genetics Receptors, Somatostatin - metabolism Scaffold Proteins Signal Transduction Somatostatin Somatostatin - genetics Somatostatin - metabolism |
| title | PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors |
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