{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:32:40Z","timestamp":1790400760078,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T00:00:00Z","timestamp":1392163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:p><jats:italic>Helicobacter pylori<\/jats:italic> strains carrying the <jats:italic>cagA<\/jats:italic> gene are associated with severe disease outcomes, most notably gastric cancer. CagA protein is delivered into gastric epithelial cells by a type <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> secretion system. The translocated CagA undergoes tyrosine phosphorylation at the C\u2010terminal <jats:styled-content style=\"fixed-case\">EPIYA<\/jats:styled-content> motifs by host cell kinases. Tyrosine\u2010phosphorylated CagA acquires the ability to interact with and activate <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>2, thereby activating mitogenic signaling and inducing cell morphological transformation (hummingbird phenotype). CagA also interacts with <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>1b via the <jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content> sequence, resulting in induction of junctional and polarity defects. Furthermore, CagA\u2010<jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>1b interaction stabilizes the CagA\u2010<jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>2 complex. Because transgenic mice systemically expressing CagA develop gastrointestinal and hematological malignancies, CagA is recognized as a bacterium\u2010derived oncoprotein. Interestingly, the C\u2010terminal region of CagA displays a large diversity among <jats:italic>H.\u00a0pylori<\/jats:italic> strains, which influences the ability of CagA to bind to <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>1b. In the present study, we investigated the biological activity of v225d CagA, an Amerindian CagA of <jats:italic>H.\u00a0pylori<\/jats:italic> isolated from a Venezuelan Piaroa Amerindian subject, because the variant CagA does not possess a canonical <jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content> sequence. We found that v225d CagA interacts with <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>2 but not <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>1b. Furthermore, <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>2\u2010binding activity of v225d CagA was much lower than that of CagA of <jats:italic>H.\u00a0pylori<\/jats:italic> isolated from Western countries (Western CagA). v225d CagA also displayed a reduced ability to induce the hummingbird phenotype than that of Western CagA. Given that perturbation of <jats:styled-content style=\"fixed-case\">PAR<\/jats:styled-content>1b and <jats:styled-content style=\"fixed-case\">SHP<\/jats:styled-content>2 by CagA underlies the oncogenic potential of CagA, the v225d strain is considered to be less oncogenic than other well\u2010studied <jats:italic>cagA<\/jats:italic>\u2010positive <jats:italic>H.\u00a0pylori<\/jats:italic> strains.<\/jats:p>","DOI":"10.1111\/cas.12342","type":"journal-article","created":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T16:10:01Z","timestamp":1387469401000},"page":"245-251","source":"Crossref","is-referenced-by-count":21,"title":["Natural variant of the <i>Helicobacter pylori<\/i> CagA oncoprotein that lost the ability to interact with <scp>PAR<\/scp>1"],"prefix":"10.1111","volume":"105","author":[{"given":"Kana","family":"Hashi","sequence":"first","affiliation":[{"name":"Division of Microbiology Graduate School of Medicine University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Murata\u2010Kamiya","sequence":"additional","affiliation":[{"name":"Division of Microbiology Graduate School of Medicine University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Varon","sequence":"additional","affiliation":[{"name":"INSERM U853 Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"M\u00e9graud","sequence":"additional","affiliation":[{"name":"INSERM U853 Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gloria","family":"Dominguez\u2010Bello","sequence":"additional","affiliation":[{"name":"Laboratory of Microbial Ecology Department of Biology University of Puerto Rico San Juan Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Hatakeyama","sequence":"additional","affiliation":[{"name":"Division of Microbiology Graduate School of Medicine University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1433"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.302.6788.1302"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199110173251603"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199110173251604"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/87.23.1777"},{"key":"e_1_2_7_7_1","first-page":"2111","article-title":"Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach","volume":"55","author":"Blaser MJ","year":"1995","journal-title":"Cancer 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