Loading…

Regulation of the CFTR channel by phosphorylation

Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are regulated tightly by protein kinases and phosphatases. The regulatory domain of CFTR has about 20 potential sites for phosphorylation by protein kinases A (PKA) and C (PKC). The reason for this large number of sites is...

Full description

Saved in:
Bibliographic Details
Published in:Pflügers Archiv 2001-01, Vol.443 Suppl 1, p.S92-S96
Main Authors: Dahan, D, Evagelidis, A, Hanrahan, J W, Hinkson, D A, Jia, Y, Luo, J, Zhu, T
Format: Article
Language:English
Subjects:
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c382t-77589b5e05760bd4b24d32a96474ee6f4fb0aaaa77cb9c1d98939372371fca313
cites
container_end_page S96
container_issue
container_start_page S92
container_title Pflügers Archiv
container_volume 443 Suppl 1
creator Dahan, D
Evagelidis, A
Hanrahan, J W
Hinkson, D A
Jia, Y
Luo, J
Zhu, T
description Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are regulated tightly by protein kinases and phosphatases. The regulatory domain of CFTR has about 20 potential sites for phosphorylation by protein kinases A (PKA) and C (PKC). The reason for this large number of sites is not known, however their conservation from fish to humans implies that they play important roles in vivo. PKA is an important activator, and its stimulation of CFTR is enhanced by PKC via mechanisms which are not fully understood. The physiological stimuli of CFTR are not known for some epithelia, and it appears likely that other serine/threonine and even tyrosine kinases also regulate CFTR in particular tissues. Phosphatases that deactivate CFTR have yet to be identified definitively at the molecular level, however CFTR is regulated by a membrane-bound form of protein phosphatase-2C (PP2C) in several cell types. Patch-clamp studies of channel rundown, co-immunoprecipitation, chemical cross-linking studies, and pull-down assays all indicate that CFTR and PP2C are closely associated within a stable regulatory complex. Understanding the regulation of CFTR by PP2C is a priority due to its potential as a target for pharmacotherapies in the treatment of cystic fibrosis.
doi_str_mv 10.1007/s004240100652
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72438958</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72438958</sourcerecordid><originalsourceid>FETCH-LOGICAL-c382t-77589b5e05760bd4b24d32a96474ee6f4fb0aaaa77cb9c1d98939372371fca313</originalsourceid><addsrcrecordid>eNpdkE1LAzEQhoMotlaPXmXx4G118rVJjlJaFQpCqeeQZLO2Zbupye6h_95IC6IDw8zh4WXmQegWwyMGEE8JgBEGea84OUNjzCgpCWB6jsYAFJeVqOQIXaW0BQDCJLlEI4wl4xTjMcJL_zm0pt-ErghN0a99MZ2vloVbm67zbWEPxX4dUu54OGLX6KIxbfI3pzlBH_PZavpaLt5f3qbPi9JRSfpSCC6V5R64qMDWzBJWU2JUxQTzvmpYY8HkEsJZ5XCtpKKKCkIFbpyhmE7QwzF3H8PX4FOvd5vkfNuazochaUEYlYrLDN7_A7dhiF2-TUvB8stc8QyVR8jFkFL0jd7Hzc7Eg8agf0TqPyIzf3cKHezO17_0yRz9BhGqawU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>874024595</pqid></control><display><type>article</type><title>Regulation of the CFTR channel by phosphorylation</title><source>Springer Link</source><creator>Dahan, D ; Evagelidis, A ; Hanrahan, J W ; Hinkson, D A ; Jia, Y ; Luo, J ; Zhu, T</creator><creatorcontrib>Dahan, D ; Evagelidis, A ; Hanrahan, J W ; Hinkson, D A ; Jia, Y ; Luo, J ; Zhu, T</creatorcontrib><description>Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are regulated tightly by protein kinases and phosphatases. The regulatory domain of CFTR has about 20 potential sites for phosphorylation by protein kinases A (PKA) and C (PKC). The reason for this large number of sites is not known, however their conservation from fish to humans implies that they play important roles in vivo. PKA is an important activator, and its stimulation of CFTR is enhanced by PKC via mechanisms which are not fully understood. The physiological stimuli of CFTR are not known for some epithelia, and it appears likely that other serine/threonine and even tyrosine kinases also regulate CFTR in particular tissues. Phosphatases that deactivate CFTR have yet to be identified definitively at the molecular level, however CFTR is regulated by a membrane-bound form of protein phosphatase-2C (PP2C) in several cell types. Patch-clamp studies of channel rundown, co-immunoprecipitation, chemical cross-linking studies, and pull-down assays all indicate that CFTR and PP2C are closely associated within a stable regulatory complex. Understanding the regulation of CFTR by PP2C is a priority due to its potential as a target for pharmacotherapies in the treatment of cystic fibrosis.</description><identifier>ISSN: 0031-6768</identifier><identifier>EISSN: 1432-2013</identifier><identifier>DOI: 10.1007/s004240100652</identifier><identifier>PMID: 11845311</identifier><language>eng</language><publisher>Germany: Springer Nature B.V</publisher><subject>Cystic fibrosis ; Cystic Fibrosis - metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism ; Humans ; Phosphoprotein Phosphatases - metabolism ; Phosphorylation ; Protein Kinases - metabolism ; Protein Phosphatase 2 ; Protein Phosphatase 2C ; Regulation ; Saccharomyces cerevisiae Proteins</subject><ispartof>Pflügers Archiv, 2001-01, Vol.443 Suppl 1, p.S92-S96</ispartof><rights>Springer-Verlag 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-77589b5e05760bd4b24d32a96474ee6f4fb0aaaa77cb9c1d98939372371fca313</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11845311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dahan, D</creatorcontrib><creatorcontrib>Evagelidis, A</creatorcontrib><creatorcontrib>Hanrahan, J W</creatorcontrib><creatorcontrib>Hinkson, D A</creatorcontrib><creatorcontrib>Jia, Y</creatorcontrib><creatorcontrib>Luo, J</creatorcontrib><creatorcontrib>Zhu, T</creatorcontrib><title>Regulation of the CFTR channel by phosphorylation</title><title>Pflügers Archiv</title><addtitle>Pflugers Arch</addtitle><description>Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are regulated tightly by protein kinases and phosphatases. The regulatory domain of CFTR has about 20 potential sites for phosphorylation by protein kinases A (PKA) and C (PKC). The reason for this large number of sites is not known, however their conservation from fish to humans implies that they play important roles in vivo. PKA is an important activator, and its stimulation of CFTR is enhanced by PKC via mechanisms which are not fully understood. The physiological stimuli of CFTR are not known for some epithelia, and it appears likely that other serine/threonine and even tyrosine kinases also regulate CFTR in particular tissues. Phosphatases that deactivate CFTR have yet to be identified definitively at the molecular level, however CFTR is regulated by a membrane-bound form of protein phosphatase-2C (PP2C) in several cell types. Patch-clamp studies of channel rundown, co-immunoprecipitation, chemical cross-linking studies, and pull-down assays all indicate that CFTR and PP2C are closely associated within a stable regulatory complex. Understanding the regulation of CFTR by PP2C is a priority due to its potential as a target for pharmacotherapies in the treatment of cystic fibrosis.</description><subject>Cystic fibrosis</subject><subject>Cystic Fibrosis - metabolism</subject><subject>Cystic Fibrosis Transmembrane Conductance Regulator - metabolism</subject><subject>Humans</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Kinases - metabolism</subject><subject>Protein Phosphatase 2</subject><subject>Protein Phosphatase 2C</subject><subject>Regulation</subject><subject>Saccharomyces cerevisiae Proteins</subject><issn>0031-6768</issn><issn>1432-2013</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNpdkE1LAzEQhoMotlaPXmXx4G118rVJjlJaFQpCqeeQZLO2Zbupye6h_95IC6IDw8zh4WXmQegWwyMGEE8JgBEGea84OUNjzCgpCWB6jsYAFJeVqOQIXaW0BQDCJLlEI4wl4xTjMcJL_zm0pt-ErghN0a99MZ2vloVbm67zbWEPxX4dUu54OGLX6KIxbfI3pzlBH_PZavpaLt5f3qbPi9JRSfpSCC6V5R64qMDWzBJWU2JUxQTzvmpYY8HkEsJZ5XCtpKKKCkIFbpyhmE7QwzF3H8PX4FOvd5vkfNuazochaUEYlYrLDN7_A7dhiF2-TUvB8stc8QyVR8jFkFL0jd7Hzc7Eg8agf0TqPyIzf3cKHezO17_0yRz9BhGqawU</recordid><startdate>20010101</startdate><enddate>20010101</enddate><creator>Dahan, D</creator><creator>Evagelidis, A</creator><creator>Hanrahan, J W</creator><creator>Hinkson, D A</creator><creator>Jia, Y</creator><creator>Luo, J</creator><creator>Zhu, T</creator><general>Springer Nature B.V</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20010101</creationdate><title>Regulation of the CFTR channel by phosphorylation</title><author>Dahan, D ; Evagelidis, A ; Hanrahan, J W ; Hinkson, D A ; Jia, Y ; Luo, J ; Zhu, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-77589b5e05760bd4b24d32a96474ee6f4fb0aaaa77cb9c1d98939372371fca313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Cystic fibrosis</topic><topic>Cystic Fibrosis - metabolism</topic><topic>Cystic Fibrosis Transmembrane Conductance Regulator - metabolism</topic><topic>Humans</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Kinases - metabolism</topic><topic>Protein Phosphatase 2</topic><topic>Protein Phosphatase 2C</topic><topic>Regulation</topic><topic>Saccharomyces cerevisiae Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dahan, D</creatorcontrib><creatorcontrib>Evagelidis, A</creatorcontrib><creatorcontrib>Hanrahan, J W</creatorcontrib><creatorcontrib>Hinkson, D A</creatorcontrib><creatorcontrib>Jia, Y</creatorcontrib><creatorcontrib>Luo, J</creatorcontrib><creatorcontrib>Zhu, T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Pflügers Archiv</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dahan, D</au><au>Evagelidis, A</au><au>Hanrahan, J W</au><au>Hinkson, D A</au><au>Jia, Y</au><au>Luo, J</au><au>Zhu, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of the CFTR channel by phosphorylation</atitle><jtitle>Pflügers Archiv</jtitle><addtitle>Pflugers Arch</addtitle><date>2001-01-01</date><risdate>2001</risdate><volume>443 Suppl 1</volume><spage>S92</spage><epage>S96</epage><pages>S92-S96</pages><issn>0031-6768</issn><eissn>1432-2013</eissn><abstract>Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are regulated tightly by protein kinases and phosphatases. The regulatory domain of CFTR has about 20 potential sites for phosphorylation by protein kinases A (PKA) and C (PKC). The reason for this large number of sites is not known, however their conservation from fish to humans implies that they play important roles in vivo. PKA is an important activator, and its stimulation of CFTR is enhanced by PKC via mechanisms which are not fully understood. The physiological stimuli of CFTR are not known for some epithelia, and it appears likely that other serine/threonine and even tyrosine kinases also regulate CFTR in particular tissues. Phosphatases that deactivate CFTR have yet to be identified definitively at the molecular level, however CFTR is regulated by a membrane-bound form of protein phosphatase-2C (PP2C) in several cell types. Patch-clamp studies of channel rundown, co-immunoprecipitation, chemical cross-linking studies, and pull-down assays all indicate that CFTR and PP2C are closely associated within a stable regulatory complex. Understanding the regulation of CFTR by PP2C is a priority due to its potential as a target for pharmacotherapies in the treatment of cystic fibrosis.</abstract><cop>Germany</cop><pub>Springer Nature B.V</pub><pmid>11845311</pmid><doi>10.1007/s004240100652</doi></addata></record>
fulltext fulltext
identifier ISSN: 0031-6768
ispartof Pflügers Archiv, 2001-01, Vol.443 Suppl 1, p.S92-S96
issn 0031-6768
1432-2013
language eng
recordid cdi_proquest_miscellaneous_72438958
source Springer Link
subjects Cystic fibrosis
Cystic Fibrosis - metabolism
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Humans
Phosphoprotein Phosphatases - metabolism
Phosphorylation
Protein Kinases - metabolism
Protein Phosphatase 2
Protein Phosphatase 2C
Regulation
Saccharomyces cerevisiae Proteins
title Regulation of the CFTR channel by phosphorylation
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T08%3A56%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Regulation%20of%20the%20CFTR%20channel%20by%20phosphorylation&rft.jtitle=Pfl%C3%BCgers%20Archiv&rft.au=Dahan,%20D&rft.date=2001-01-01&rft.volume=443%20Suppl%201&rft.spage=S92&rft.epage=S96&rft.pages=S92-S96&rft.issn=0031-6768&rft.eissn=1432-2013&rft_id=info:doi/10.1007/s004240100652&rft_dat=%3Cproquest_cross%3E72438958%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c382t-77589b5e05760bd4b24d32a96474ee6f4fb0aaaa77cb9c1d98939372371fca313%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=874024595&rft_id=info:pmid/11845311&rfr_iscdi=true