{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:55:05Z","timestamp":1791176105708,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"content-version":"vor","delay-in-days":407,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Mammalian sperm were previously shown to express the PP1\u03b32 isoform of protein phosphatase 1 (PP1) as well as its regulatory proteins inhibitor 2 and glycogen synthase kinase 3. Furthermore, the development of sperm motility during transit through the epididymis correlates with changes in PP1 activity. Thus, since PP1 cellular activity is determined by the partners it binds, we embarked on a study aimed at defining the specific interactomes of PP1\u03b31 and PP1\u03b32 (the two known alternatively spliced variants of PP1\u03b3). To this end, exhaustive screens were performed on a human testis cDNA library using the yeast two\u2010hybrid method. Among the various proteins detected, the most abundant interactors with PP1\u03b32 were Nek2A and R15B. Closer sequence analysis revealed novel alternatively spliced variants of Nek2A and NIPP1, which we designated Nek2A\u2010T and NIPP1\u2010T, respectively. They were shown to be highly expressed in rat and human testis by Northern analysis and to result from alternative splicing events by RT\u2010PCR. Thus, both the previously known Nek2A isoform and the novel Nek2A\u2010T and NIPP1\u2010T variants appear to bind PP1\u03b32 <jats:italic>in vitro<\/jats:italic> (blot overlays) and <jats:italic>in vivo<\/jats:italic> by coexpression in yeast. The usefulness of testis\u2010specific alternatively spliced proteins as targets for the development of novel therapeutic strategies for male infertility and contraception is discussed. PP1\u03b32, Nek2A\u2010T, and NIPP1\u2010T are currently being investigated as alternatively spliced targets for signal transduction therapeutics.<\/jats:p>","DOI":"10.1196\/annals.1329.059","type":"journal-article","created":{"date-parts":[[2005,1,19]],"date-time":"2005-01-19T23:57:53Z","timestamp":1106179073000},"page":"468-478","source":"Crossref","is-referenced-by-count":32,"title":["Alternatively Spliced Protein Variants as Potential Therapeutic Targets for Male Infertility and Contraception"],"prefix":"10.1111","volume":"1030","author":[{"given":"MARGARIDA","family":"FARDILHA","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WENJUAN","family":"WU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ROS\u00c1LIA","family":"S\u00c1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SARA","family":"FIDALGO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CRISTINA","family":"SOUSA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CATARINA","family":"MOTA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ODETE A.B.","family":"DA CRUZ E SILVA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EDGAR F.","family":"DA CRUZ E SILVA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,7,8]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)02176-4"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/418236a"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00210743"},{"key":"e_1_2_5_5_2","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1523\/JNEUROSCI.15-05-03375.1995","article-title":"Differential expression of protein phosphatase 1 isoforms in mammalian brain","volume":"15","author":"Cruz e Silva E.F.","year":"1995","journal-title":"J. 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