{"created":"2021-03-01T06:18:56.582155+00:00","id":2336,"links":{},"metadata":{"_buckets":{"deposit":"abfc1ac8-9cbe-4964-825b-d06c9fb882df"},"_deposit":{"id":"2336","owners":[],"pid":{"revision_id":0,"type":"depid","value":"2336"},"status":"published"},"_oai":{"id":"oai:repository.dl.itc.u-tokyo.ac.jp:00002336"},"item_7_alternative_title_1":{"attribute_name":"\u305d\u306e\u4ed6\u306e\u30bf\u30a4\u30c8\u30eb","attribute_value_mlt":[{"subitem_alternative_title":"G\u30bf\u30f3\u30d1\u30af\u8cea\u5171\u5f79\u578b\u53d7\u5bb9\u4f53G2A : \u907a\u4f1d\u5b50\u767a\u73fe\u304a\u3088\u3073\u7d30\u80de\u5185\u6a5f\u80fd\u89e3\u6790"}]},"item_7_biblio_info_7":{"attribute_name":"\u66f8\u8a8c\u60c5\u5831","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2009-03-23","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{}]}]},"item_7_date_granted_25":{"attribute_name":"\u5b66\u4f4d\u6388\u4e0e\u5e74\u6708\u65e5","attribute_value_mlt":[{"subitem_dategranted":"2009-03-23"}]},"item_7_degree_grantor_23":{"attribute_name":"\u5b66\u4f4d\u6388\u4e0e\u6a5f\u95a2","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"University of Tokyo (\u6771\u4eac\u5927\u5b66)"}]}]},"item_7_degree_name_20":{"attribute_name":"\u5b66\u4f4d\u540d","attribute_value_mlt":[{"subitem_degreename":"\u535a\u58eb(\u533b\u5b66)"}]},"item_7_description_5":{"attribute_name":"\u6284\u9332","attribute_value_mlt":[{"subitem_description":"G-protein coupled receptors (GPCRs) play pivotal roles in almost all the physiological and pathological conditions. However, many of the receptors remain as \u201corphan\u201d receptors, whose ligand(s) are unknown. G2A (named for G2 accumulation in cell cycle) was one of these orphan receptors, whose constitutive activity makes the identification of the ligand(s) difficult. The aim of this study is to identify the ligand(s) of hG2A and to characterize the cellular function of the receptor, through investigating the intracellular signaling and the transcriptional regulation.// The findings in this PhD thesis consist of two major parts. First, human G2A (hG2A) is activated by extracellular low pH, though it shows significant activity at physiological condition of pH 7.4 (constitutive activity). The pH-dependent activation evoked by hG2A is Rho-dependent, which is completely inhibited by C3-toxin, and partially by the expression of dominant negative Rho. Considering the structural homology with Ovarian cancer G-protein coupled receptor 1 (OGR1/GPR68), another member of G2A family, the acid-sensing ability is attributed to the conserved histidine residue H174, as H174F mutant exhibits less pH-dependent activity compared with wild type receptor. In addition, lysophosphatidylcholine (LPC), a proposed agonist for G2A, actually inhibited pH-dependent activity at IC50 of 3 \u03bcM. Second, transcriptional regulation of hG2A in THP-1, a monocytic cell line, is dependent both on the chromatin structure around the transcriptional start site (TSS), and on the transcription factors\u2019 (c/EBP\u03b1 and \u03b2, Runx1 and Pu.1) binding to their cis-elements, located at the core promoter just upstream of TSS.","subitem_description_type":"Abstract"}]},"item_7_dissertation_number_26":{"attribute_name":"\u5b66\u4f4d\u6388\u4e0e\u756a\u53f7","attribute_value_mlt":[{"subitem_dissertationnumber":"\u7532\u7b2c24772\u53f7"}]},"item_7_full_name_3":{"attribute_name":"\u8457\u8005\u5225\u540d","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"6542","nameIdentifierScheme":"WEKO"}],"names":[{"name":"\u30e0\u30e9\u30ab\u30df, \u30ca\u30aa\u30ab"}]}]},"item_7_identifier_registration":{"attribute_name":"ID\u767b\u9332","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15083/00002330","subitem_identifier_reg_type":"JaLC"}]},"item_7_select_21":{"attribute_name":"\u5b66\u4f4d","attribute_value_mlt":[{"subitem_select_item":"doctoral"}]},"item_7_text_22":{"attribute_name":"\u5b66\u4f4d\u5206\u91ce","attribute_value_mlt":[{"subitem_text_value":"Medical Science (\u533b\u5b66)"}]},"item_7_text_24":{"attribute_name":"\u7814\u7a76\u79d1\u30fb\u5c02\u653b","attribute_value_mlt":[{"subitem_text_value":"Department of Molecular Cell Biology, Graduate School of Medicine (\u533b\u5b66\u7cfb\u7814\u7a76\u79d1\u5206\u5b50\u7d30\u80de\u751f\u7269\u5b66\u5c02\u653b)"}]},"item_7_text_27":{"attribute_name":"\u5b66\u4f4d\u8a18\u756a\u53f7","attribute_value_mlt":[{"subitem_text_value":"\u535a\u533b\u7b2c3192\u53f7"}]},"item_7_text_4":{"attribute_name":"\u8457\u8005\u6240\u5c5e","attribute_value_mlt":[{"subitem_text_value":"\u6771\u4eac\u5927\u5b66\u5927\u5b66\u9662\u533b\u5b66\u7cfb\u7814\u7a76\u79d1\u5206\u5b50\u7d30\u80de\u751f\u7269\u5b66\u5c02\u653b"}]},"item_creator":{"attribute_name":"\u8457\u8005","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"\u6751\u4e0a, \u5c1a\u52a0"}],"nameIdentifiers":[{"nameIdentifier":"6541","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"\u30d5\u30a1\u30a4\u30eb\u60c5\u5831","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-05-31"}],"displaytype":"detail","filename":"41_57518.pdf","filesize":[{"value":"62.1 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"41_57518.pdf","url":"https://repository.dl.itc.u-tokyo.ac.jp/record/2336/files/41_57518.pdf"},"version_id":"cdbd6800-0c66-4fc6-897e-7f1863c8c07f"}]},"item_language":{"attribute_name":"\u8a00\u8a9e","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"\u8cc7\u6e90\u30bf\u30a4\u30d7","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Characterization of human G2A : gene regulation and cellular function","item_titles":{"attribute_name":"\u30bf\u30a4\u30c8\u30eb","attribute_value_mlt":[{"subitem_title":"Characterization of human G2A : gene regulation and cellular function"}]},"item_type_id":"7","owner":"1","path":["9/233/280","125/358/359"],"pubdate":{"attribute_name":"\u516c\u958b\u65e5","attribute_value":"2012-03-01"},"publish_date":"2012-03-01","publish_status":"0","recid":"2336","relation_version_is_last":true,"title":["Characterization of human G2A : gene regulation and cellular function"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2021-03-01T20:08:06.375990+00:00"}