C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins
MRP2, a member of the ABC protein superfamily, functions as an ATP-dependent export pump for anionic conjugates in the apical membranes of epithelial cells. It has been reported that the trafficking of MRP2 is modulated by PKC. Adjacent to the C-terminal PDZ binding motif, which may be involved in t...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2003-03, Vol.302 (3), p.454-461 |
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| creator | Hegedüs, Tamás Sessler, Tamás Scott, Robert Thelin, William Bakos, Éva Váradi, András Szabó, Katalin Homolya, László Milgram, Sharon L. Sarkadi, Balázs |
| description | MRP2, a member of the ABC protein superfamily, functions as an ATP-dependent export pump for anionic conjugates in the apical membranes of epithelial cells. It has been reported that the trafficking of MRP2 is modulated by PKC. Adjacent to the C-terminal PDZ binding motif, which may be involved in the targeting of MRP2, we found a potential PKC phosphorylation site (Ser
1542). Therefore, we examined the interaction of MRP2 and its phosphorylation-mimicking mutants with different PDZ proteins (EBP50, E3KARP, PDZK1, IKEPP, β2-syntrophin, and SAP-97). The binding of these PDZ proteins to CFTR and ABCA1, other ABC proteins, possessing PDZ binding motif, was also studied. We observed a strong binding of apically localized PDZ proteins to both MRP2 and CFTR, whereas β2-syntrophin exhibited binding only to ABCA1. The phosphorylation-mimicking MRP2 mutant and a phosphorylated C-terminal MRP2 peptide showed significantly increased binding to IKEPP, EBP50, and both individual PDZ domains of EBP50. Our results suggest that phosphorylation of the MRP2 PDZ binding motif has a profound effect on the PDZ binding of MRP2. |
| doi_str_mv | 10.1016/S0006-291X(03)00196-7 |
| format | Article |
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1542). Therefore, we examined the interaction of MRP2 and its phosphorylation-mimicking mutants with different PDZ proteins (EBP50, E3KARP, PDZK1, IKEPP, β2-syntrophin, and SAP-97). The binding of these PDZ proteins to CFTR and ABCA1, other ABC proteins, possessing PDZ binding motif, was also studied. We observed a strong binding of apically localized PDZ proteins to both MRP2 and CFTR, whereas β2-syntrophin exhibited binding only to ABCA1. The phosphorylation-mimicking MRP2 mutant and a phosphorylated C-terminal MRP2 peptide showed significantly increased binding to IKEPP, EBP50, and both individual PDZ domains of EBP50. Our results suggest that phosphorylation of the MRP2 PDZ binding motif has a profound effect on the PDZ binding of MRP2.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/S0006-291X(03)00196-7</identifier><identifier>PMID: 12615054</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Motifs ; Animals ; Blotting, Western ; Dose-Response Relationship, Drug ; Humans ; Insecta ; Mitochondrial Proteins ; MRP2 ; PDZ ; Peptides - chemistry ; Peptides - pharmacology ; Phosphorylation ; Plasmids - metabolism ; Protein Binding ; Protein Structure, Tertiary ; Protein–protein interaction ; Ribosomal Proteins - chemistry ; Ribosomal Proteins - metabolism ; Saccharomyces cerevisiae Proteins ; Serine - metabolism</subject><ispartof>Biochemical and biophysical research communications, 2003-03, Vol.302 (3), p.454-461</ispartof><rights>2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-db65192871d7c85e7b4d5b485c4baeaa846582bc46cb9541720c9ef1f892ca5b3</citedby><cites>FETCH-LOGICAL-c444t-db65192871d7c85e7b4d5b485c4baeaa846582bc46cb9541720c9ef1f892ca5b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X03001967$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12615054$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hegedüs, Tamás</creatorcontrib><creatorcontrib>Sessler, Tamás</creatorcontrib><creatorcontrib>Scott, Robert</creatorcontrib><creatorcontrib>Thelin, William</creatorcontrib><creatorcontrib>Bakos, Éva</creatorcontrib><creatorcontrib>Váradi, András</creatorcontrib><creatorcontrib>Szabó, Katalin</creatorcontrib><creatorcontrib>Homolya, László</creatorcontrib><creatorcontrib>Milgram, Sharon L.</creatorcontrib><creatorcontrib>Sarkadi, Balázs</creatorcontrib><title>C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>MRP2, a member of the ABC protein superfamily, functions as an ATP-dependent export pump for anionic conjugates in the apical membranes of epithelial cells. It has been reported that the trafficking of MRP2 is modulated by PKC. Adjacent to the C-terminal PDZ binding motif, which may be involved in the targeting of MRP2, we found a potential PKC phosphorylation site (Ser
1542). Therefore, we examined the interaction of MRP2 and its phosphorylation-mimicking mutants with different PDZ proteins (EBP50, E3KARP, PDZK1, IKEPP, β2-syntrophin, and SAP-97). The binding of these PDZ proteins to CFTR and ABCA1, other ABC proteins, possessing PDZ binding motif, was also studied. We observed a strong binding of apically localized PDZ proteins to both MRP2 and CFTR, whereas β2-syntrophin exhibited binding only to ABCA1. The phosphorylation-mimicking MRP2 mutant and a phosphorylated C-terminal MRP2 peptide showed significantly increased binding to IKEPP, EBP50, and both individual PDZ domains of EBP50. Our results suggest that phosphorylation of the MRP2 PDZ binding motif has a profound effect on the PDZ binding of MRP2.</description><subject>Amino Acid Motifs</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Dose-Response Relationship, Drug</subject><subject>Humans</subject><subject>Insecta</subject><subject>Mitochondrial Proteins</subject><subject>MRP2</subject><subject>PDZ</subject><subject>Peptides - chemistry</subject><subject>Peptides - pharmacology</subject><subject>Phosphorylation</subject><subject>Plasmids - metabolism</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>Protein–protein interaction</subject><subject>Ribosomal Proteins - chemistry</subject><subject>Ribosomal Proteins - metabolism</subject><subject>Saccharomyces cerevisiae Proteins</subject><subject>Serine - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkNtKxDAQhoMo7rr6CEqvRC-qkzRJ2yuR9QjrAQ8g3oQ0nWKkhzXpKvv2xt1FL70YBobvnx8-QnYpHFGg8vgRAGTMcvpyAMkhAM1lnK6RIYUcYkaBr5PhLzIgW96_B4hymW-SAWWSChB8SG7HcY-usa2uo-lb58O4ea1727VRV0U3D_csarpyFk7oI9uHaUNAmwXxZfu36P7sNZq6rkfb-m2yUena485qj8jzxfnT-Cqe3F1ej08nseGc93FZSEFzlqW0TE0mMC14KQqeCcMLjVpnXIqMFYZLU-SC05SBybGiVZYzo0WRjMj-8m8o_pih71VjvcG61i12M6_SBGSSAPwL0ixNeCJZAMUSNK7z3mGlps422s0VBfVjXC2Mqx-dChK1MB56RmRvVTArGiz_UivFAThZAhh8fFp0yhuLrcHSOjS9Kjv7T8U3cWCQYg</recordid><startdate>20030314</startdate><enddate>20030314</enddate><creator>Hegedüs, Tamás</creator><creator>Sessler, Tamás</creator><creator>Scott, Robert</creator><creator>Thelin, William</creator><creator>Bakos, Éva</creator><creator>Váradi, András</creator><creator>Szabó, Katalin</creator><creator>Homolya, László</creator><creator>Milgram, Sharon L.</creator><creator>Sarkadi, Balázs</creator><general>Elsevier Inc</general><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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030314</creationdate><title>C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins</title><author>Hegedüs, Tamás ; Sessler, Tamás ; Scott, Robert ; Thelin, William ; Bakos, Éva ; Váradi, András ; Szabó, Katalin ; Homolya, László ; Milgram, Sharon L. ; Sarkadi, Balázs</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-db65192871d7c85e7b4d5b485c4baeaa846582bc46cb9541720c9ef1f892ca5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amino Acid Motifs</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Dose-Response Relationship, Drug</topic><topic>Humans</topic><topic>Insecta</topic><topic>Mitochondrial Proteins</topic><topic>MRP2</topic><topic>PDZ</topic><topic>Peptides - chemistry</topic><topic>Peptides - pharmacology</topic><topic>Phosphorylation</topic><topic>Plasmids - metabolism</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>Protein–protein interaction</topic><topic>Ribosomal Proteins - chemistry</topic><topic>Ribosomal Proteins - metabolism</topic><topic>Saccharomyces cerevisiae Proteins</topic><topic>Serine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hegedüs, Tamás</creatorcontrib><creatorcontrib>Sessler, Tamás</creatorcontrib><creatorcontrib>Scott, Robert</creatorcontrib><creatorcontrib>Thelin, William</creatorcontrib><creatorcontrib>Bakos, Éva</creatorcontrib><creatorcontrib>Váradi, András</creatorcontrib><creatorcontrib>Szabó, Katalin</creatorcontrib><creatorcontrib>Homolya, László</creatorcontrib><creatorcontrib>Milgram, Sharon L.</creatorcontrib><creatorcontrib>Sarkadi, Balázs</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hegedüs, Tamás</au><au>Sessler, Tamás</au><au>Scott, Robert</au><au>Thelin, William</au><au>Bakos, Éva</au><au>Váradi, András</au><au>Szabó, Katalin</au><au>Homolya, László</au><au>Milgram, Sharon L.</au><au>Sarkadi, Balázs</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2003-03-14</date><risdate>2003</risdate><volume>302</volume><issue>3</issue><spage>454</spage><epage>461</epage><pages>454-461</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>MRP2, a member of the ABC protein superfamily, functions as an ATP-dependent export pump for anionic conjugates in the apical membranes of epithelial cells. It has been reported that the trafficking of MRP2 is modulated by PKC. Adjacent to the C-terminal PDZ binding motif, which may be involved in the targeting of MRP2, we found a potential PKC phosphorylation site (Ser
1542). Therefore, we examined the interaction of MRP2 and its phosphorylation-mimicking mutants with different PDZ proteins (EBP50, E3KARP, PDZK1, IKEPP, β2-syntrophin, and SAP-97). The binding of these PDZ proteins to CFTR and ABCA1, other ABC proteins, possessing PDZ binding motif, was also studied. We observed a strong binding of apically localized PDZ proteins to both MRP2 and CFTR, whereas β2-syntrophin exhibited binding only to ABCA1. The phosphorylation-mimicking MRP2 mutant and a phosphorylated C-terminal MRP2 peptide showed significantly increased binding to IKEPP, EBP50, and both individual PDZ domains of EBP50. Our results suggest that phosphorylation of the MRP2 PDZ binding motif has a profound effect on the PDZ binding of MRP2.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12615054</pmid><doi>10.1016/S0006-291X(03)00196-7</doi><tpages>8</tpages></addata></record> |
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| subjects | Amino Acid Motifs Animals Blotting, Western Dose-Response Relationship, Drug Humans Insecta Mitochondrial Proteins MRP2 PDZ Peptides - chemistry Peptides - pharmacology Phosphorylation Plasmids - metabolism Protein Binding Protein Structure, Tertiary Protein–protein interaction Ribosomal Proteins - chemistry Ribosomal Proteins - metabolism Saccharomyces cerevisiae Proteins Serine - metabolism |
| title | C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins |
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