{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:05:28Z","timestamp":1793156728830,"version":"4.5.0"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"31","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,7,31]]},"abstract":"\n Focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, displays phosphorylation-dependent localization in the seminiferous epithelium of adult rat testes. FAK is an integrated component of the blood\u2013testis barrier (BTB) involved in regulating Sertoli cell adhesion via its effects on the occludin\u2013zonula occludens-1 complex. Herein, we report that p-FAK-Tyr\n 407<\/jats:sup>\n and p-FAK-Tyr\n 397<\/jats:sup>\n display restricted spatiotemporal and almost mutually exclusive localization in the epithelium, affecting BTB dynamics antagonistically, with the former promoting and the latter disrupting the Sertoli cell tight junction\u2013permeability barrier function. Using primary cultured Sertoli cells as an in vitro model that mimics the BTB in vivo both functionally and ultrastructurally, effects of FAK phosphorylation on BTB function were studied by expressing nonphosphorylatable and phosphomimetic mutants, with tyrosine replaced by phenylalanine (F) and glutamate (E), respectively. Compared with WT FAK, Y407E and Y397F mutations each promoted barrier function, and the promoting effect of the Y407E mutant was abolished in the Y397E-Y407E double mutant, demonstrating antagonism between Tyr\n 407<\/jats:sup>\n and Tyr\n 397<\/jats:sup>\n . Furthermore, Y407E mutation induced the recruitment of actin-related protein 3 to the Sertoli cell-cell interface, where it became more tightly associated with neuronal Wiskott\u2013Aldrich syndrome protein, promoting actin-related protein 2\/3 complex activity. Conversely, Y407F mutation reduced the rate of actin polymerization at the Sertoli cell BTB. In summary, FAK-Tyr\n 407<\/jats:sup>\n phosphorylation promotes BTB integrity by strengthening the actin filament-based cytoskeleton. FAK serves as a bifunctional molecular \u201cswitch\u201d to direct the cyclical disassembly and reassembly of the BTB during the epithelial cycle of spermatogenesis, depending on its phosphorylation status, to facilitate the transit of preleptotene spermatocytes across the BTB.\n <\/jats:p>","DOI":"10.1073\/pnas.1202316109","type":"journal-article","created":{"date-parts":[[2012,7,14]],"date-time":"2012-07-14T05:47:32Z","timestamp":1342244852000},"page":"12562-12567","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["Focal adhesion kinase-Tyr\n 407<\/sup>\n and -Tyr\n 397<\/sup>\n exhibit antagonistic effects on blood\u2013testis barrier dynamics in the rat"],"prefix":"10.1073","volume":"109","author":[{"given":"Pearl P. Y.","family":"Lie","sequence":"first","affiliation":[{"name":"The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores D.","family":"Mruk","sequence":"additional","affiliation":[{"name":"The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Wai","family":"Mok","sequence":"additional","affiliation":[{"name":"The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Su","sequence":"additional","affiliation":[{"name":"The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will M.","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Yan","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,7,12]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002790"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.71"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-221035"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06867"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4161\/spmg.1.1.14525"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813113106"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1549"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.05.006"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.045112"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2011.08.001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2026"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310739200"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1626"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609302200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.02.010"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-191-8_16"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2006.08.011"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2004.03.011"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/cm.20241"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302381200"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200608010"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1094"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280902998413"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb829"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.070623"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513218200"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711264105"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1202316109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T21:18:48Z","timestamp":1649798328000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1202316109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,12]]},"references-count":27,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2012,7,31]]}},"alternative-id":["10.1073\/pnas.1202316109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1202316109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,12]]},"assertion":[{"value":"2012-07-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}