{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:06:04Z","timestamp":1790539564801,"version":"4.1.0"},"reference-count":57,"publisher":"Portland Press Ltd.","issue":"17","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,16]]},"abstract":"<jats:p>Apicomplexan parasites like Toxoplasma gondii grow and replicate within a specialized organelle called the parasitophorous vacuole. The vacuole is decorated with parasite proteins that integrate into the membrane after trafficking through the parasite secretory system as soluble, chaperoned complexes. A regulator of this process is an atypical protein kinase called WNG1. Phosphorylation by WNG1 appears to serve as a switch for membrane integration. However, like its substrates, WNG1 is secreted from the parasite dense granules, and its activity must, therefore, be tightly regulated until the correct membrane is encountered. Here, we demonstrate that, while another member of the WNG family can adopt multiple multimeric states, WNG1 is monomeric and therefore not regulated by multimerization. Instead, we identify two phosphosites on WNG1 that are required for its kinase activity. Using a combination of in vitro biochemistry and structural modeling, we identify basic residues that are also required for WNG1 activity and appear to recognize the activating phosphosites. Among these coordinating residues are the \u2018HRD\u2019 Arg, which recognizes activation loop phosphorylation in canonical kinases. WNG1, however, is not phosphorylated on its activation loop, but rather on atypical phosphosites on its C-lobe. We propose a simple model in which WNG1 is activated by increasing ATP concentration above a critical threshold once the kinase traffics to the parasitophorous vacuole.<\/jats:p>","DOI":"10.1042\/bcj20220076","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T09:44:06Z","timestamp":1659951846000},"page":"1877-1889","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Divergent kinase WNG1 is regulated by phosphorylation of an atypical activation sub-domain"],"prefix":"10.1042","volume":"479","author":[{"given":"Pravin S.","family":"Dewangan","sequence":"first","affiliation":[{"name":"1Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsebaot G.","family":"Beraki","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Ariana","family":"Paiz","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Appiah Mensah","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, TX, U.S.A."},{"name":"2Honors College, University of Texas at Dallas, Richardson, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"3Department of Biophysics, University of Texas, Southwestern Medical Center, Dallas, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-9594","authenticated-orcid":false,"given":"Michael L.","family":"Reese","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, TX, U.S.A."},{"name":"4Department of Biochemistry, University of Texas, Southwestern Medical Center, Dallas, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"2022091612400585600_BCJ-2022-0076C1","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1126\/science.1075762","article-title":"The protein kinase complement of the human genome","volume":"298","year":"2002","journal-title":"Science"},{"key":"2022091612400585600_BCJ-2022-0076C2","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/0092-8674(91)90098-J","article-title":"ERKs: a family of protein-serine\/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF","volume":"65","year":"1991","journal-title":"Cell"},{"key":"2022091612400585600_BCJ-2022-0076C3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1126\/science.2164259","article-title":"An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control","volume":"249","year":"1990","journal-title":"Science"},{"key":"2022091612400585600_BCJ-2022-0076C4","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1073\/pnas.85.11.3753","article-title":"Insulin-stimulated microtubule-associated protein kinase is phosphorylated on tyrosine and threonine in vivo","volume":"85","year":"1988","journal-title":"Proc. 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