{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:33:15Z","timestamp":1791113595794,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,2,17]],"date-time":"2012-02-17T00:00:00Z","timestamp":1329436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Ge 905\/13\u20101"],"award-info":[{"award-number":["Ge 905\/13\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["14\u20101"],"award-info":[{"award-number":["14\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p>\n                    Recently it was shown that the mineralocorticoid receptor (MR) may exert part of its transcriptional activity by mediation of calcineurin (PP2B). Here we investigated the mechanism of interaction of MR with calcineurin and provide a new MR signaling pathway with potential physiological and pathophysiological relevance. MR \u2192 calcineurin crosstalk was assessed in a heterologous expression system (human embryonic kidney cells), which provides the opportunity for detailed mechanistic investigation. SiRNA knockdown experiments show that activated MR, but not GR, reduces CREB\u2010 and enhances NFaT\u2010mediated transcriptional activation\n                    <jats:italic>via<\/jats:italic>\n                    the catalytic calcineurin subunit PP2BA\u03b2 but not\n                    <jats:italic>via<\/jats:italic>\n                    PP2BA\u03b1. Altered PP2BA\u03b2 expression, elevated cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , activation of mitogen\u2010activated kinase [p38, extracellular signal\u2010regulated kinase (ERK) 1\/2], or protein kinase C do not seem to be involved, whereas inhibition of the chaperone heat\u2010shock protein 90 (HSP90) abrogated the effect of MR Coimmunoprecipitation indicates the existence of protein complexes harboring MR and PP2BA\u03b2 independent of MR activation but dependent on HSP90. Activated MR alters the subcellular distribution of PP2BA\u03b2, enhancing its nuclear fraction, and reduces mRNA expression of the endogenous inhibitor CAIN (calcineurin inhibitor) but not of RCAN1 (regulator of calcineurin). Overall, transcriptional relevant MR \u2192 calcineurin crosstalk occurs\n                    <jats:italic>via<\/jats:italic>\n                    the catalytic subunit PP2BA\u03b2, enables glucocorticoid response element\u2010independent genomic signaling of MR, and is of potential pathophysiological relevance. Mechanistically, the crosstalk results from HSP90\u2010mediated cytosolic protein complex formation, altered subcellular distribution, and altered endogenous inhibitor expression.\u2014Seiferth, A., Ruhs, S., Mildenberger, S., Gekle, M., Grossmann, C. The phosphatase calcineurin PP2BA\u03b2 mediates part of mineralocorticoid receptor.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 2327\u20102337 (2012).\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.11-199976","type":"journal-article","created":{"date-parts":[[2012,2,17]],"date-time":"2012-02-17T21:29:31Z","timestamp":1329514171000},"page":"2327-2337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The phosphatase calcineurin PP2BA\u03b2 mediates part of mineralocorticoid receptor transcriptional activity"],"prefix":"10.1096","volume":"26","author":[{"given":"Anja","family":"Seiferth","sequence":"first","affiliation":[{"name":"Julius\u2010Bernstein\u2010Institut f\u00fcr Physiologie Universit\u00e4t 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