{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:51:36Z","timestamp":1768873896962,"version":"3.49.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"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":[[2008,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Crg1 and Crg2 are regulators of G-protein signaling homologs found in the human fungal pathogen\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            . Crg1 negatively regulates pheromone responses and mating through direct inhibition of G\u03b1 subunits Gpa2 and Gpa3. It has also been proposed that Crg2 has a role in mating, as genetic crosses involving\n            <jats:italic>\u0394crg2<\/jats:italic>\n            mutants resulted in formation of hyperfilaments. We found that mutation of Gpa2 and Gpa3 partially suppressed the hyperfilamentation, mutation of Gpa3 alleviated\n            <jats:italic>\u0394crg2<\/jats:italic>\n            -specfic cell swelling, and mutation of the mitogen-activated protein kinase Cpk1 blocked both processes. These findings indicate that Gpa2 and Gpa3 function downstream of Crg2 and that Gpa3 is also epistatic to Crg2 in a Cpk1-dependent morphogenesis process linked to mating. Significantly, we found that\n            <jats:italic>\u0394crg2<\/jats:italic>\n            mutants formed enlarged capsules that mimic cells expressing a constitutively active\n            <jats:italic>GPA1<\/jats:italic>\n            (\n            <jats:italic>Q284L<\/jats:italic>\n            ) allele and that the levels of intracellular cyclic AMP (cAMP) were also elevated, suggesting that Crg2 also negatively regulates the Gpa1-cAMP signaling pathway. We further showed that Crg2 interacted with Gpa3 and Gpa1, but not Gpa2, in a pulldown assay and that Crg2 maintained a higher in vitro GTPase-activating protein activity toward Gpa3 and Gpa1 than to Gpa2. Finally, we found that dysregulation of cAMP due to the Crg2 mutation attenuated virulence in a murine model of cryptococcosis. Taken together, our study reveals Crg2 as an RGS (regulator of G-protein signaling) protein of multiregulatory function, including one that controls mating distinctly from Crg1 and one that serves as a novel inhibitor of Gpa1-cAMP signaling.\n          <\/jats:p>","DOI":"10.1128\/ec.00154-08","type":"journal-article","created":{"date-parts":[[2008,7,26]],"date-time":"2008-07-26T00:45:29Z","timestamp":1217033129000},"page":"1540-1548","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["The RGS Protein Crg2 Regulates Pheromone and Cyclic AMP Signaling in\n            <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"7","author":[{"given":"Gui","family":"Shen","sequence":"first","affiliation":[{"name":"The Research Institute for Children"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Li","family":"Wang","sequence":"additional","affiliation":[{"name":"The Research Institute for Children"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Whittington","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, Immunology, and Parasitology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lie","family":"Li","sequence":"additional","affiliation":[{"name":"The Research Institute for Children"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"The Research Institute for Children"},{"name":"Departments of Microbiology, Immunology, and Parasitology"},{"name":"Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70118"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3206"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.1.75-84.2002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9729965"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.6.1476-1491.2004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.5.2.330-346.2006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03563.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01515-9"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.40.1.235"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.7.12.4169-4177.1987"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.7.3871"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.9.3179-3191.2001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.10.5684"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2003.11.021"},{"key":"e_1_3_2_15_2","first-page":"1585","volume":"9","year":"1997","unstructured":"Gold, S. 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