{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:32:17Z","timestamp":1790875937570,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,6,10]]},"abstract":"<jats:p>\n                    Phosphatidylinositol lipids play diverse physiological roles, and their concentrations are tightly regulated by various kinases and phosphatases. The enzymatic activity of\n                    <jats:italic>Ciona intestinalis<\/jats:italic>\n                    voltage sensor-containing phosphatase (Ci-VSP), recently identified as a member of the PTEN (phosphatase and tensin homolog deleted on chromosome 10) family of phosphatidylinositol phosphatases, is regulated by its own voltage-sensor domain in a voltage-dependent manner. However, a detailed mechanism of Ci-VSP regulation and its substrate specificity remain unknown. Here we determined the\n                    <jats:italic>in vitro<\/jats:italic>\n                    substrate specificity of Ci-VSP by measuring the phosphoinositide phosphatase activity of the Ci-VSP cytoplasmic phosphatase domain. Despite the high degree of identity shared between the active sites of PTEN and Ci-VSP, Ci-VSP dephosphorylates not only the PTEN substrate, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P\n                    <jats:sub>3<\/jats:sub>\n                    ], but also, unlike PTEN, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    ]. Enzymatic action on PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    removes the phosphate at position 5 of the inositol ring, resulting in the production of phosphatidylinositol 4-phosphate [PI(4)P]. The active site Cys-X\n                    <jats:sub>5<\/jats:sub>\n                    -Arg (CX\n                    <jats:sub>5<\/jats:sub>\n                    R) sequence of Ci-VSP differs with that of PTEN only at amino acid 365 where a glycine residue in Ci-VSP is replaced by an alanine in PTEN. Ci-VSP with a G365A mutation no longer dephosphorylates PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    and is not capable of inducing depolarization-dependent rundown of a PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    -dependent potassium channel. These results indicate that Ci-VSP is a PI(3,4,5)P\n                    <jats:sub>3<\/jats:sub>\n                    \/PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    phosphatase that uniquely functions in the voltage-dependent regulation of ion channels through regulation of PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    levels.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0803936105","type":"journal-article","created":{"date-parts":[[2008,6,4]],"date-time":"2008-06-04T21:20:59Z","timestamp":1212614459000},"page":"7970-7975","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":130,"title":["A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate"],"prefix":"10.1073","volume":"105","author":[{"given":"Hirohide","family":"Iwasaki","sequence":"first","affiliation":[{"name":"Section for Developmental Neurophysiology, Okazaki Center for Integrative Biosciences, and"},{"name":"National Institute for Physiological Sciences, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi 4448787, Japan;"},{"name":"Graduate University for Advanced Studies (Sokendai), Hayama-cho, Miura-gun, Kanagawa 2400193, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimichi","family":"Murata","sequence":"additional","affiliation":[{"name":"Section for Developmental Neurophysiology, Okazaki Center for Integrative Biosciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngjun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0721; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Israil","family":"Hossain","sequence":"additional","affiliation":[{"name":"Section for Developmental Neurophysiology, Okazaki Center for Integrative Biosciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A.","family":"Worby","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0721; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack E.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0721; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"McCormack","sequence":"additional","affiliation":[{"name":"Section for Developmental Neurophysiology, Okazaki Center for Integrative Biosciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Immunology, Akita University School of Medicine, 1-1-1 Hondo, Akita-shi, Akita 0108543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Okamura","sequence":"additional","affiliation":[{"name":"Section for Developmental Neurophysiology, Okazaki Center for Integrative Biosciences, and"},{"name":"National Institute for Physiological Sciences, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi 4448787, Japan;"},{"name":"Graduate University for Advanced Studies (Sokendai), Hayama-cho, Miura-gun, Kanagawa 2400193, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,6,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200603156"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/BC20050081"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2006.03.007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.071403.161303"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.8.1439"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.13375"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.247"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03650"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.02.006"},{"key":"e_1_3_3_10_2","first-page":"875","article-title":"Depolarization activates the phosphoinositide phosphatase Ci-VSP, as detected in Xenopus oocytes coexpressing sensors of PIP2","volume":"583","author":"Murata Y","year":"2007","unstructured":"Y Murata, Y Okamura, Depolarization activates the phosphoinositide phosphatase Ci-VSP, as detected in Xenopus oocytes coexpressing sensors of PIP2. J Phys 583, 875\u2013889 (2007).","journal-title":"J Phys"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2000.4497"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01519-6"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01625-2"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/35882"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00125-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2005.05.005"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0222-6"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.143.2.501"},{"key":"e_1_3_3_19_2","first-page":"cm3","article-title":"PI3K class IB pathway in neutrophils","volume":"2007","author":"Andrews S","year":"2007","unstructured":"S Andrews, LR Stephens, PT Hawkins, PI3K class IB pathway in neutrophils. Sci STKE 2007, cm3 (2007).","journal-title":"Sci STKE"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2006.10.013"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(03)74799-7"},{"key":"e_1_3_3_22_2","first-page":"399","article-title":"A testis-specific gene, TPTE, encodes a putative transmembrane tyrosine phosphatase and maps to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22, and Y","volume":"105","author":"Chen H","year":"1999","unstructured":"H Chen, et al., A testis-specific gene, TPTE, encodes a putative transmembrane tyrosine phosphatase and maps to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22, and Y. Hum Genet 105, 399\u2013409 (1999).","journal-title":"Hum Genet"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3600277"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101480200"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706184200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00033.2003"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.10.6066"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(92)90137-6"},{"key":"e_1_3_3_29_2","first-page":"217","article-title":"Assaying phosphoinositide phosphatases","volume":"284","author":"Taylor GS","year":"2004","unstructured":"GS Taylor, JE Dixon, Assaying phosphoinositide phosphatases. Methods Mol Biol 284, 217\u2013227 (2004).","journal-title":"Methods Mol Biol"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(92)07017-I"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0803936105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:58:35Z","timestamp":1649782715000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0803936105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,10]]},"references-count":30,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2008,6,10]]}},"alternative-id":["10.1073\/pnas.0803936105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0803936105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,10]]},"assertion":[{"value":"2008-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}