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Several studies have identified gain\u2010of\u2010function mutations of\n                    <jats:italic>TRPC6<\/jats:italic>\n                    and report induced expression and enhanced channel activity of TRPC6 in association with glomerular diseases. Interfering with TRPC6 activity may open novel therapeutic pathways. TRPC6 channel activity is controlled by protein expression and stability as well as intracellular trafficking. Identification of regulatory phosphorylation sites in TRPC6 and corresponding protein kinases is essential to understand the regulation of TRPC6 activity and may result in future therapeutic strategies. In this study, an unbiased phosphoproteomic screen of human TRPC6 identified several novel serine phosphorylation sites. The phosphorylation site at serine 14 of TRPC6 is embedded in a basophilic kinase motif that is highly conserved across species. We confirmed serine 14 as a target of MAPKs and proline\u2010directed kinases like cyclin\u2010dependent kinase 5 (Cdk5) in cell\u2010based as well as\n                    <jats:italic>in vitro<\/jats:italic>\n                    kinase assays and quantitative phosphoproteomic analysis of TRPC6. Phosphorylation of TRPC6 at serine 14 enhances channel conductance by boosting membrane expression of TRPC6, whereas protein stability and multimerization of TRPC6 are not altered, making serine 14 phosphorylation a potential drug target to interfere with TRPC6 channel activity.\u2014Hagmann, H., Mangold, N., Rinschen, M. M., Koenig, T., Kunzelmann, K., Schermer, B., Benzing, T., Brinkkoetter, P. T. Proline\u2010dependent and basophilic kinases phosphorylate human TRPC6 at serine 14 to control channel activity through increased membrane expression. FASEB J. 32,208\u2010219 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700309r","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T00:30:45Z","timestamp":1504744245000},"page":"208-219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Proline\u2010dependent and basophilic kinases phosphorylate human TRPC6 at serine 14 to control channel activity through increased membrane expression"],"prefix":"10.1096","volume":"32","author":[{"given":"Henning","family":"Hagmann","sequence":"first","affiliation":[{"name":"Department II of Internal Medicine, Center for Molecular Medicine Cologne, University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Mangold","sequence":"additional","affiliation":[{"name":"Department II of Internal Medicine, Center for Molecular Medicine Cologne, University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus M.","family":"Rinschen","sequence":"additional","affiliation":[{"name":"Department II of Internal Medicine, Center for Molecular Medicine Cologne, University of Cologne Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Response in Aging\u2010Associated Diseases (CECAD), University of Cologne Cologne Germany"},{"name":"Systems Biology of Ageing Cologne (Sybacol), University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Koenig","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Response in Aging\u2010Associated Diseases (CECAD), University of Cologne Cologne Germany"},{"name":"Institute for Genetics Cologne Excellence Cluster on Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD), University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Kunzelmann","sequence":"additional","affiliation":[{"name":"Department of Physiology University Regensburg Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard","family":"Schermer","sequence":"additional","affiliation":[{"name":"Department II of Internal Medicine, Center for Molecular Medicine Cologne, University of Cologne Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Response in Aging\u2010Associated Diseases (CECAD), University of Cologne Cologne Germany"},{"name":"Systems Biology of Ageing Cologne (Sybacol), University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Benzing","sequence":"additional","affiliation":[{"name":"Department II of Internal Medicine, Center for Molecular Medicine Cologne, University of Cologne Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Response in Aging\u2010Associated Diseases (CECAD), University of Cologne Cologne Germany"},{"name":"Systems Biology of Ageing Cologne (Sybacol), University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul T.","family":"Brinkkoetter","sequence":"additional","affiliation":[{"name":"Department II of Internal Medicine, Center for Molecular Medicine Cologne, University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,9,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00298.2010"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-119495"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2006"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603930200"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27702"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601417"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8110com"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.07.062"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106215"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/ng1592","article-title":"TRPC6 is a glomerular slit diaphragm\u2014associated channel required for normal renal function.","volume":"37","author":"Polu K R.","year":"2005","journal-title":"Nat. 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