{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:56:58Z","timestamp":1791284218663,"version":"4.1.0"},"reference-count":25,"publisher":"Cambridge University Press (CUP)","issue":"4","license":[{"start":{"date-parts":[[2003,10,17]],"date-time":"2003-10-17T00:00:00Z","timestamp":1066348800000},"content-version":"unspecified","delay-in-days":16,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:p>Praziquantel, the drug of choice against schistosomiasis, disrupts calcium (Ca<jats:sup>2+<\/jats:sup>) homeostasis in schistosomes via an unknown mechanism. Voltage-gated Ca<jats:sup>2+<\/jats:sup> channels are heteromultimeric transmembrane protein complexes that contribute to impulse propagation and also regulate intracellular Ca<jats:sup>2+<\/jats:sup> levels. \u03b2 subunits modulate the properties of the pore-forming \u03b1<jats:sub>1<\/jats:sub> subunit of high voltage-activated Ca<jats:sup>2+<\/jats:sup> channels. Unlike other Ca<jats:sup>2+<\/jats:sup> channel \u03b2 subunits, which have current stimulatory effects, a \u03b2 subunit subtype found in <jats:italic>S. mansoni<\/jats:italic> (<jats:italic>Sm<\/jats:italic>\u03b2A) and <jats:italic>S. japonicum<\/jats:italic> (<jats:italic>Sj<\/jats:italic>\u03b2) dramatically reduces current levels when co-expressed with Ca<jats:sup>2+<\/jats:sup> channel \u03b1<jats:sub>1<\/jats:sub> subunits in <jats:italic>Xenopus<\/jats:italic> oocytes. It also confers praziquantel sensitivity to the mammalian Ca<jats:sub>v<\/jats:sub>2.3 \u03b1<jats:sub>1<\/jats:sub> subunit. The Beta Interaction Domains (BIDs) of <jats:italic>Sm<\/jats:italic>\u03b2A and <jats:italic>Sj<\/jats:italic>\u03b2 lack 2 conserved serines that each constitute a consensus site for protein kinase C (PKC) phosphorylation. Here, we use site-directed mutagenesis of schistosome \u03b2 subunits to show that these unique functional properties are correlated with the absence of these consensus PKC sites in the BID. Furthermore, a second schistosome \u03b2 subunit subtype contains both serines in the BID, enhances currents through \u03b1<jats:sub>1<\/jats:sub> subunits, and does not confer praziquantel sensitivity. Thus, phosphorylation sites in the BID may play important roles in defining the modulatory properties and pharmacological sensitivities of schistosome Ca<jats:sup>2+<\/jats:sup> channel \u03b2 subunits.<\/jats:p>","DOI":"10.1017\/s003118200300386x","type":"journal-article","created":{"date-parts":[[2003,10,17]],"date-time":"2003-10-17T09:42:34Z","timestamp":1066383754000},"page":"349-356","source":"Crossref","is-referenced-by-count":49,"title":["Specific sites in the Beta Interaction Domain of a schistosome Ca<sup>2+<\/sup> channel \u03b2 subunit are key to its role in sensitivity to the anti-schistosomal drug praziquantel"],"prefix":"10.1017","volume":"127","author":[{"given":"A. B.","family":"KOHN","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"ROBERTS-MISTERLY","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. A. V.","family":"ANDERSON","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"KHAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. M.","family":"GREENBERG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2003,10,17]]},"reference":[{"key":"S003118200300386X_ref023","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.22.4673"},{"key":"S003118200300386X_ref019","doi-asserted-by":"publisher","DOI":"10.1021\/bi970500d"},{"key":"S003118200300386X_ref006","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90363-8"},{"key":"S003118200300386X_ref002","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021989622656"},{"key":"S003118200300386X_ref003","doi-asserted-by":"crossref","unstructured":"BOURINET, E. , ZAMPONI, G. W. , STEA, A. , SOONG, T. W. , LEWIS, B. A. , JONES, L. P. , YUE, D. T. & SNUTCH, T. P. (1996).The \u03b11E calcium channel exhibits permeation properties similar to low-voltage-activated calcium channels.Journal of Neuroscience 16, 4983\u20134993.","DOI":"10.1523\/JNEUROSCI.16-16-04983.1996"},{"key":"S003118200300386X_ref004","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.521"},{"key":"S003118200300386X_ref010","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02098-6"},{"key":"S003118200300386X_ref005","doi-asserted-by":"publisher","DOI":"10.1016\/0169-4758(92)90070-I"},{"key":"S003118200300386X_ref008","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0033648"},{"key":"S003118200300386X_ref009","unstructured":"JEZIORSKI, M. C. , GREENBERG, R. M. & ANDERSON, P. A. V. (1999).Cloning and expression of a jellyfish calcium channel \u03b2 subunit reveal functional conservation of the \u03b11-\u03b2 interaction.Receptors and Channels 6, 375\u2013386."},{"key":"S003118200300386X_ref011","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.112.2.125"},{"key":"S003118200300386X_ref012","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.12.1095"},{"key":"S003118200300386X_ref013","unstructured":"KEEF, K. D. , HUME, J. R. & ZHONG, J. (2001).Regulation of cardiac and smooth muscle Ca2+ channels (Cav1.2a,b) by protein kinases.American Journal of Physiology: Cell Physiology 281, C1743\u2013C1755."},{"key":"S003118200300386X_ref014","doi-asserted-by":"crossref","unstructured":"KOHN, A. B. , ANDERSON, P. A. V. , ROBERTS-MISTERLY, J. M. & GREENBERG, R. M. (2001 a).Schistosome calcium channel \u03b2 subunits: unusual modulatory effects and potential role in the action of the antischistosomal drug praziquantel.Journal of Biological Chemistry 276, 36873\u201336876.","DOI":"10.1074\/jbc.C100273200"},{"key":"S003118200300386X_ref016","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/17.12.1244"},{"key":"S003118200300386X_ref017","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-280-5:003"},{"key":"S003118200300386X_ref018","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90428-6"},{"key":"S003118200300386X_ref020","doi-asserted-by":"publisher","DOI":"10.1016\/0169-4758(96)80640-5"},{"key":"S003118200300386X_ref024","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01200-9"},{"key":"S003118200300386X_ref021","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-7952(99)80004-4"},{"key":"S003118200300386X_ref022","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1703"},{"key":"S003118200300386X_ref025","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.8.4720"},{"key":"S003118200300386X_ref015","doi-asserted-by":"crossref","unstructured":"KOHN, A. B. , LEA, J. M. , ROBERTS-MISTERLY, J. M. , ANDERSON, P. A. V. & GREENBERG, R. M. (2001 b).Structure of three high voltage-activated Ca2+ channel \u03b11 subunits from Schistosoma mansoni .Parasitology 123, 489\u2013497.","DOI":"10.1017\/S0031182001008691"},{"key":"S003118200300386X_ref007","doi-asserted-by":"publisher","DOI":"10.1021\/bi0119565"},{"key":"S003118200300386X_ref001","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(85)90020-8"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S003118200300386X","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T18:29:56Z","timestamp":1557167396000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S003118200300386X\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,10]]}},"alternative-id":["S003118200300386X"],"URL":"https:\/\/doi.org\/10.1017\/s003118200300386x","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10]]}}}