Phosphorylation-Dependent Regulation of Ryanodine Receptors: A Novel Role for Leucine/Isoleucine Zippers
Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including R...
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| Veröffentlicht in: | The Journal of cell biology 2001-05, Vol.153 (4), p.699-708 |
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| container_title | The Journal of cell biology |
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| creator | Marx, Steven O. Reiken, Steven Hisamatsu, Yuji Gaburjakova, Marta Gaburjakova, Jana Yang, Yi-Ming Rosemblit, Nora Marks, Andrew R. |
| description | Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function. |
| doi_str_mv | 10.1083/jcb.153.4.699 |
| format | Article |
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Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.153.4.699</identifier><identifier>PMID: 11352932</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies ; Base Sequence ; Binding sites ; Calcium Channels - metabolism ; Carrier Proteins - metabolism ; Cellular biology ; Complementary DNA ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Dogs ; Gene expression regulation ; Heart ; Ion channels ; Ions ; Isoleucine - metabolism ; Leucine Zippers - physiology ; Membrane Proteins - metabolism ; Molecular Sequence Data ; Mutagenesis, Site-Directed - physiology ; Myocardium - enzymology ; Original ; Phosphatases ; Phosphoprotein Phosphatases - metabolism ; Phosphorylation ; Physiological regulation ; Proteins ; Receptors ; Ryanodine Receptor Calcium Release Channel - genetics ; Ryanodine Receptor Calcium Release Channel - metabolism ; Skeletal muscle</subject><ispartof>The Journal of cell biology, 2001-05, Vol.153 (4), p.699-708</ispartof><rights>Copyright 2001 The Rockefeller University Press</rights><rights>Copyright Rockefeller University Press May 14, 2001</rights><rights>2001 The Rockefeller University Press 2001 The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11352932$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marx, Steven O.</creatorcontrib><creatorcontrib>Reiken, Steven</creatorcontrib><creatorcontrib>Hisamatsu, Yuji</creatorcontrib><creatorcontrib>Gaburjakova, Marta</creatorcontrib><creatorcontrib>Gaburjakova, Jana</creatorcontrib><creatorcontrib>Yang, Yi-Ming</creatorcontrib><creatorcontrib>Rosemblit, Nora</creatorcontrib><creatorcontrib>Marks, Andrew R.</creatorcontrib><title>Phosphorylation-Dependent Regulation of Ryanodine Receptors: A Novel Role for Leucine/Isoleucine Zippers</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Base Sequence</subject><subject>Binding sites</subject><subject>Calcium Channels - metabolism</subject><subject>Carrier Proteins - metabolism</subject><subject>Cellular biology</subject><subject>Complementary DNA</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Dogs</subject><subject>Gene expression regulation</subject><subject>Heart</subject><subject>Ion channels</subject><subject>Ions</subject><subject>Isoleucine - metabolism</subject><subject>Leucine Zippers - physiology</subject><subject>Membrane Proteins - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed - physiology</subject><subject>Myocardium - enzymology</subject><subject>Original</subject><subject>Phosphatases</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Phosphorylation</subject><subject>Physiological regulation</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Ryanodine Receptor Calcium Release Channel - genetics</subject><subject>Ryanodine Receptor Calcium Release Channel - metabolism</subject><subject>Skeletal muscle</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctLw0AQxhdRtFaP3kQWD97S7jPJehBKfRWKStGLl7BJJzYhzcbdpND_3sXW51x2-ObHx3w7CJ1QMqAk5sMySwdU8oEYhErtoB6VggQxFWQX9QhhNFCSyQN06FxJCBGR4PvogFIumeKshxZPC-OahbHrSreFqYNraKCeQ93iGbx1GxGbHM_WujbzogavZ9C0xrpLPMIPZgUVnpkKcG4snkKXeWY4cV75bPFr0TRg3RHay3Xl4Hj79tHL7c3z-D6YPt5NxqNpUHJB2yClkhHtS0SpVJnioZ7nwKSIScoiImMfKZV5DFqTOBIZUMZ1KuIwJWGkQfM-utr4Nl26hHnmk1hdJY0tltquE6OL5O-kLhbJm1kljCrGFfUGF1sDa947cG2yLFwGVaVrMJ1LaMxCJUnowfN_YGk6W_tw3isiUSQF99DZ73W-9_i6gAdON0Dp_J_-zEPmj0X5B1mqky8</recordid><startdate>20010514</startdate><enddate>20010514</enddate><creator>Marx, Steven O.</creator><creator>Reiken, Steven</creator><creator>Hisamatsu, Yuji</creator><creator>Gaburjakova, Marta</creator><creator>Gaburjakova, Jana</creator><creator>Yang, Yi-Ming</creator><creator>Rosemblit, Nora</creator><creator>Marks, Andrew R.</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20010514</creationdate><title>Phosphorylation-Dependent Regulation of Ryanodine Receptors: A Novel Role for Leucine/Isoleucine Zippers</title><author>Marx, Steven O. ; Reiken, Steven ; Hisamatsu, Yuji ; Gaburjakova, Marta ; Gaburjakova, Jana ; Yang, Yi-Ming ; Rosemblit, Nora ; Marks, Andrew R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j341t-b1520aaaa47b59c936adfe25480b27058021b5f8eaa0874ce123ab486b067aea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Base Sequence</topic><topic>Binding sites</topic><topic>Calcium Channels - metabolism</topic><topic>Carrier Proteins - metabolism</topic><topic>Cellular biology</topic><topic>Complementary DNA</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Dogs</topic><topic>Gene expression regulation</topic><topic>Heart</topic><topic>Ion channels</topic><topic>Ions</topic><topic>Isoleucine - metabolism</topic><topic>Leucine Zippers - physiology</topic><topic>Membrane Proteins - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed - physiology</topic><topic>Myocardium - enzymology</topic><topic>Original</topic><topic>Phosphatases</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Phosphorylation</topic><topic>Physiological regulation</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Ryanodine Receptor Calcium Release Channel - genetics</topic><topic>Ryanodine Receptor Calcium Release Channel - metabolism</topic><topic>Skeletal muscle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marx, Steven O.</creatorcontrib><creatorcontrib>Reiken, Steven</creatorcontrib><creatorcontrib>Hisamatsu, Yuji</creatorcontrib><creatorcontrib>Gaburjakova, Marta</creatorcontrib><creatorcontrib>Gaburjakova, Jana</creatorcontrib><creatorcontrib>Yang, Yi-Ming</creatorcontrib><creatorcontrib>Rosemblit, Nora</creatorcontrib><creatorcontrib>Marks, Andrew R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marx, Steven O.</au><au>Reiken, Steven</au><au>Hisamatsu, Yuji</au><au>Gaburjakova, Marta</au><au>Gaburjakova, Jana</au><au>Yang, Yi-Ming</au><au>Rosemblit, Nora</au><au>Marks, Andrew R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphorylation-Dependent Regulation of Ryanodine Receptors: A Novel Role for Leucine/Isoleucine Zippers</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2001-05-14</date><risdate>2001</risdate><volume>153</volume><issue>4</issue><spage>699</spage><epage>708</epage><pages>699-708</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>Ryanodine receptors (RyRs), intracellular calcium release channels required for cardiac and skeletal muscle contraction, are macromolecular complexes that include kinases and phosphatases. Phosphorylation/dephosphorylation plays a key role in regulating the function of many ion channels, including RyRs. However, the mechanism by which kinases and phosphatases are targeted to ion channels is not well understood. We have identified a novel mechanism involved in the formation of ion channel macromolecular complexes: kinase and phosphatase targeting proteins binding to ion channels via leucine/isoleucine zipper (LZ) motifs. Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents phosphorylation of RyR2. Elucidation of this new role for LZs in ion channel macromolecular complexes now permits: (a) rapid mapping of kinase and phosphatase targeting protein binding sites on ion channels; (b) predicting which kinases and phosphatases are likely to regulate a given ion channel; (c) rapid identification of novel kinase and phosphatase targeting proteins; and (d) tools for dissecting the role of kinases and phosphatases as modulators of ion channel function.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>11352932</pmid><doi>10.1083/jcb.153.4.699</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Animals Antibodies Base Sequence Binding sites Calcium Channels - metabolism Carrier Proteins - metabolism Cellular biology Complementary DNA Cyclic AMP-Dependent Protein Kinases - metabolism Dogs Gene expression regulation Heart Ion channels Ions Isoleucine - metabolism Leucine Zippers - physiology Membrane Proteins - metabolism Molecular Sequence Data Mutagenesis, Site-Directed - physiology Myocardium - enzymology Original Phosphatases Phosphoprotein Phosphatases - metabolism Phosphorylation Physiological regulation Proteins Receptors Ryanodine Receptor Calcium Release Channel - genetics Ryanodine Receptor Calcium Release Channel - metabolism Skeletal muscle |
| title | Phosphorylation-Dependent Regulation of Ryanodine Receptors: A Novel Role for Leucine/Isoleucine Zippers |
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