{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:13:37Z","timestamp":1791400417460,"version":"4.3.3"},"reference-count":0,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1995,4,1]]},"abstract":"<jats:p> Genistein, a protein tyrosine kinase inhibitor, activates the cystic fibrosis transmembrane conductance regulator (CFTR) in transfected NIH-3T3 fibroblasts that express the CFTR (3T3-CFTR). CFTR activity was assayed by 125I efflux and by patch clamping in the cell-attached mode. Both forskolin and genistein stimulated 125I efflux and activated a 9-10 pS anion channel in 3T3-CFTR cells but failed to activate 125I efflux in mock-transfected NIH-3T3 cells. Genistein, unlike forskolin and 3-isobutyl-1-methylxanthine, did not increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) above control levels. This demonstrates that genistein-dependent activation does not involve inhibition of phosphodiesterase activity and suggests that stimulation does not involve a direct activation of protein kinase A. Genistein stimulated 125I efflux to approximately 50% of the maximal rate with forskolin. Genistein did not increase 125I efflux at saturating forskolin but decreased the concentration of forskolin required for half-maximal stimulation. Orthovanadate (VO4), a phosphotyrosine phosphatase inhibitor, inhibited genistein-induced channel activation with an inhibition constant of approximately 20 microM. These effects suggest that, in addition to activation by protein kinase A, the CFTR is regulated by a tyrosine kinase-dependent pathway. <\/jats:p>","DOI":"10.1152\/ajpcell.1995.268.4.c886","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T18:39:42Z","timestamp":1514140782000},"page":"C886-C893","source":"Crossref","is-referenced-by-count":172,"title":["cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein"],"prefix":"10.1152","volume":"268","author":[{"given":"B.","family":"Illek","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California,Berkeley 94720, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California,Berkeley 94720, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. F.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California,Berkeley 94720, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. H.","family":"Widdicombe","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California,Berkeley 94720, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. E.","family":"Machen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California,Berkeley 94720, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. W.","family":"Reenstra","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California,Berkeley 94720, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.1995.268.4.C886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:37:42Z","timestamp":1718653062000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.1995.268.4.C886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,4,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1995,4,1]]}},"alternative-id":["10.1152\/ajpcell.1995.268.4.C886"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.1995.268.4.c886","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,4,1]]}}}