{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:30:13Z","timestamp":1787016613498,"version":"build-2736575974"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Entamoeba histolytica<\/jats:named-content>\n                    is a protozoan parasite that causes amoebic dysentery and liver abscess.\n                    <jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>\n                    relies on motility, phagocytosis, host cell adhesion, and proteolysis of extracellular matrix for virulence. In eukaryotic cells, these processes are mediated in part by phosphatidylinositol 3-kinase (PI3K) signaling. Thus, PI3K may be critical for virulence. We utilized a functional genomics approach to identify genes whose products may operate in the PI3K pathway in\n                    <jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>\n                    . We treated a population of trophozoites that were overexpressing genes from a cDNA library with a near-lethal dose of the PI3K inhibitor wortmannin. This screen was based on the rationale that survivors would be overexpressing gene products that directly or indirectly function in the PI3K pathway. We sequenced the overexpressed genes in survivors and identified a cDNA encoding a Rap GTPase, a protein previously shown to participate in the PI3K pathway. This supports the validity of our approach. Genes encoding a coactosin-like protein, EhCoactosin, and a serine-rich\n                    <jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>\n                    protein (SREHP) were also identified. Cells overexpressing EhCoactosin or SREHP were also less sensitive to a second PI3K inhibitor, LY294002. This corroborates the link between these proteins and PI3K. Finally, a mutant cell line with an increased level of phosphatidylinositol (3,4,5)-triphosphate, the product of PI3K activity, exhibited increased expression of SREHP and EhCoactosin. This further supports the functional connection between these proteins and PI3K in\n                    <jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>\n                    . To our knowledge, this is the first forward-genetics screen adapted to reveal genes participating in a signal transduction pathway in this pathogen.\n                  <\/jats:p>","DOI":"10.1128\/ec.00329-13","type":"journal-article","created":{"date-parts":[[2014,1,17]],"date-time":"2014-01-17T23:02:55Z","timestamp":1389999775000},"page":"401-411","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["A Genomewide Overexpression Screen Identifies Genes Involved in the Phosphatidylinositol 3-Kinase Pathway in the Human Protozoan Parasite Entamoeba histolytica"],"prefix":"10.1128","volume":"13","author":[{"given":"Amrita B.","family":"Koushik","sequence":"first","affiliation":[{"name":"Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA"},{"name":"Eukaryotic Pathogens Innovation Center (EPIC), Clemson University, Clemson, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda H.","family":"Welter","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"},{"name":"Eukaryotic Pathogens Innovation Center (EPIC), Clemson University, Clemson, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Rock","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"},{"name":"Eukaryotic Pathogens Innovation Center (EPIC), Clemson University, Clemson, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesly A.","family":"Temesvari","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA"},{"name":"Eukaryotic Pathogens Innovation Center (EPIC), Clemson University, Clemson, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"97","article-title":"Amoebiasis","volume":"72","author":"World Health Organization.","year":"1997","unstructured":"World Health Organization. 1997. 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