{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:06:52Z","timestamp":1767625612680},"reference-count":57,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2002,4,1]],"date-time":"2002-04-01T00:00:00Z","timestamp":1017619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2002,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid\n            <jats:italic>MAT<\/jats:italic>\n            \u03b1 and\n            <jats:italic>MAT<\/jats:italic>\n            a cells. Virulence has been linked to the mating type, and\n            <jats:italic>MAT<\/jats:italic>\n            \u03b1 cells are more virulent than congenic\n            <jats:italic>MAT<\/jats:italic>\n            a cells. To study the link between the mating type and virulence, we functionally analyzed three genes encoding homologs of the p21-activated protein kinase family:\n            <jats:italic>STE20<\/jats:italic>\n            \u03b1,\n            <jats:italic>STE20<\/jats:italic>\n            a, and\n            <jats:italic>PAK1<\/jats:italic>\n            . In contrast to the\n            <jats:italic>STE20<\/jats:italic>\n            genes that were previously shown to be in the mating-type locus, the\n            <jats:italic>PAK1<\/jats:italic>\n            gene is unlinked to the mating type. The\n            <jats:italic>STE20<\/jats:italic>\n            \u03b1,\n            <jats:italic>STE20<\/jats:italic>\n            a, and\n            <jats:italic>PAK1<\/jats:italic>\n            genes were disrupted in serotype A and D strains of\n            <jats:italic>C. neoformans<\/jats:italic>\n            , revealing central but distinct roles in mating, differentiation, cytokinesis, and virulence.\n            <jats:italic>ste20<\/jats:italic>\n            \u03b1\n            <jats:italic>pak1<\/jats:italic>\n            and\n            <jats:italic>ste20<\/jats:italic>\n            a\n            <jats:italic>pak1<\/jats:italic>\n            double mutants were synthetically lethal, indicating that these related kinases share an essential function. In summary, our studies identify an association between the\n            <jats:italic>STE20<\/jats:italic>\n            \u03b1 gene, the\n            <jats:italic>MAT<\/jats:italic>\n            \u03b1 locus, and virulence in a serotype A clinical isolate and provide evidence that PAK kinases function in a MAP kinase signaling cascade controlling the mating, differentiation, and virulence of this fungal pathogen.\n          <\/jats:p>","DOI":"10.1128\/ec.1.2.257-272.2002","type":"journal-article","created":{"date-parts":[[2002,12,5]],"date-time":"2002-12-05T01:41:58Z","timestamp":1039052518000},"page":"257-272","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":98,"title":["Mating-Type-Specific and Nonspecific PAK Kinases Play Shared and Divergent Roles in\n            <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"1","author":[{"given":"Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connie B.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus B.","family":"Lengeler","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"the Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E.","family":"Cardenas","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary M.","family":"Cox","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Perfect","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[{"name":"Departments of Molecular Genetics and Microbiology"},{"name":"Medicine"},{"name":"Pharmacology and Cancer Biology"},{"name":"the Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01852.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000060352"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3206"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.1.75-84.2002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.24.4563"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.2.926-928.2000"},{"key":"e_1_3_2_8_2","unstructured":"Cryptococcus neoformans 1998"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.5.871"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02375.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.15.1817"},{"key":"e_1_3_2_12_2","first-page":"1","volume":"39","year":"2000","unstructured":"Davidson, R. 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