{"id":950,"date":"2026-03-08T14:59:34","date_gmt":"2026-03-08T14:59:34","guid":{"rendered":"http:\/\/wmtc2006.com\/?p=950"},"modified":"2026-03-08T14:59:34","modified_gmt":"2026-03-08T14:59:34","slug":"two-lines-of-transgenic-founders-were-shown-line-1-and-line-4","status":"publish","type":"post","link":"https:\/\/wmtc2006.com\/?p=950","title":{"rendered":"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4)"},"content":{"rendered":"

\ufeffTwo lines of transgenic founders were shown (line 1 and line 4). Flow cytometry analysis was carried out using antibodies specific for CD4, CD8, TCR and other activation markers (CD69, CD25, HSA). and peripheral T cells. Proliferation of peripheral T cells is reduced but apoptosis of DP cells and subsequent T cell maturation, including regulatory T cells, are normal. AKT phosphorylation can be readily observed in most wild-type T cell compartments but not DP thymocytes in response to TCR activation. Thus, the PI3K-AKT pathway is crucial for the transition of ISP to DP thymocytes but is dispensable for apoptosis and maturation of developing thymocytes. Keywords:PTEN, Thymocytes, AKT, proliferation, apoptosis == Introduction == Activation of the PI3K pathway by growth factor receptors is one of the major signaling events leading to growth, proliferation and anti-apoptosis. PI3K activation results in an increase of the lipid phosphatidylinositol-3,4,5-triphosphate, which recruits lipid-binding domain containing kinases PDK1 and AKT to the membrane [1-3]. PDK1 activates AKT [4] and SGK, a serum and glucocorticoid-induced kinase with a similar structure to AKT. AKT has many direct substrates, including the cell cycle inhibitor p27, Foxo family of transcription factors, the pro-apoptotic Bcl-2 family protein Bad and TSC1, a protein that inhibits the TOR pathway [2,4]. Phosphorylation of these substrates by AKT leads to cell cycle entry, resistance to apoptosis, increase in cell size and other growth-related events. Bitopertin Unlike AKT, SGK has more restricted substrates but it also phosphorylates the Foxo family of transcription factors to promote cell survival and cell cycle entry [5]. Regulation of the PI3K signaling pathway is important for normal differentiation; its dysregulation can lead to cancer. PTEN is Bitopertin<\/a> a lipid phosphatase and a major negative regulator of the PI3K pathway [2,6,7]. Loss of PTEN in both alleles is frequently found in many human cancer cells. Germline heterozygous mutation of PTEN is present in patients with the Cowden syndrome [8,9], who develop hyperplastic lesions in multiple organs with increased risks of cancer. In mice, heterozygous mutation of PTEN Bitopertin eventually leads to development of malignancy in different organs, including thymus, prostate, thyroid, liver and intestines [10-12]. In T cells, conditional knockout of PTEN exhibits defective apoptosis of developing thymocytes and appearance of aggressive lymphomas, resulting in mouse lethality by 15 weeks of age [13-15]. Development of tumors is preceded by activation of the PI3K pathway in the PTEN-deficient T cell precursors of these mice, including AKT phosphorylation, Foxo3a phosphorylation and reduced levels of p27 [15]. In the lymphoid system, the PI3K pathway has been shown to be important for optimal immune responses. It mediates signaling from the co-stimulatory T cell molecule CD28 and B cell docking molecules like CD19 [16-18]. During T cell development, the PI3K-AKT activities are required for the selection checkpoint. Deletion of PDK1 or a combination of Akt1 and Akt2, two of the three AKT family members, results in a partial Rabbit Polyclonal to MDM4 (phospho-Ser367)<\/a> blockage at the DN (Double Negative CD4-CD8-) to DP (Double Positive) stage [19,20]. Interestingly in Akt1-\/-Akt2-\/-thymocytes, the block at DN stage is not due to inhibition of proliferation but rather because of the loss of resistance to apoptosis when cells receive the pre-TCR signals [20]. Similarly, deletion of both PI3K catalytic subunits and results in a drastic reduction of the DP thymocyte human population [21]. Although improved apoptosis of DP cells in these animals was reported [21], the problems are more likely to be similar to that of Akt1-\/-Akt2-\/-mice with increased apoptosis of DN human population as the main culprit. Because of the early block in DN to DP transition state in PDK1, Akt1\/Akt2 or PIK3 \/ knockout mice, it has not been possible to properly assess the part of the PI3K-AKT.<\/p>\n","protected":false},"excerpt":{"rendered":"

\ufeffTwo lines of transgenic founders were shown (line 1 and line 4). Flow cytometry analysis was carried out using antibodies specific for CD4, CD8, TCR […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[23],"tags":[],"class_list":["post-950","post","type-post","status-publish","format-standard","hentry","category-histamine-receptors"],"yoast_head":"\n\ufeffTwo lines of transgenic founders were shown (line 1 and line 4) - Discovery and characterization of Histamine-2 Receptor Antagonists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/wmtc2006.com\/?p=950\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4) - Discovery and characterization of Histamine-2 Receptor Antagonists\" \/>\n<meta property=\"og:description\" content=\"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4). Flow cytometry analysis was carried out using antibodies specific for CD4, CD8, TCR [...]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/wmtc2006.com\/?p=950\" \/>\n<meta property=\"og:site_name\" content=\"Discovery and characterization of Histamine-2 Receptor Antagonists\" \/>\n<meta property=\"article:published_time\" content=\"2026-03-08T14:59:34+00:00\" \/>\n<meta name=\"author\" content=\"wpadmin\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"wpadmin\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/wmtc2006.com\\\/?p=950#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/wmtc2006.com\\\/?p=950\"},\"author\":{\"name\":\"wpadmin\",\"@id\":\"http:\\\/\\\/wmtc2006.com\\\/#\\\/schema\\\/person\\\/5a1d916d8ed9c89b34ac45c96f81e776\"},\"headline\":\"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4)\",\"datePublished\":\"2026-03-08T14:59:34+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/wmtc2006.com\\\/?p=950\"},\"wordCount\":635,\"articleSection\":[\"Histamine Receptors\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/wmtc2006.com\\\/?p=950\",\"url\":\"https:\\\/\\\/wmtc2006.com\\\/?p=950\",\"name\":\"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4) - Discovery and characterization of Histamine-2 Receptor Antagonists\",\"isPartOf\":{\"@id\":\"http:\\\/\\\/wmtc2006.com\\\/#website\"},\"datePublished\":\"2026-03-08T14:59:34+00:00\",\"author\":{\"@id\":\"http:\\\/\\\/wmtc2006.com\\\/#\\\/schema\\\/person\\\/5a1d916d8ed9c89b34ac45c96f81e776\"},\"breadcrumb\":{\"@id\":\"https:\\\/\\\/wmtc2006.com\\\/?p=950#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/wmtc2006.com\\\/?p=950\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/wmtc2006.com\\\/?p=950#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"http:\\\/\\\/wmtc2006.com\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4)\"}]},{\"@type\":\"WebSite\",\"@id\":\"http:\\\/\\\/wmtc2006.com\\\/#website\",\"url\":\"http:\\\/\\\/wmtc2006.com\\\/\",\"name\":\"Discovery and characterization of Histamine-2 Receptor Antagonists\",\"description\":\"Just another WordPress site\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"http:\\\/\\\/wmtc2006.com\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"http:\\\/\\\/wmtc2006.com\\\/#\\\/schema\\\/person\\\/5a1d916d8ed9c89b34ac45c96f81e776\",\"name\":\"wpadmin\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/e57206ca88c051844b618224f501afdd8e9328b238000fd2f37bf30c03bcff14?s=96&d=mm&r=g\",\"url\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/e57206ca88c051844b618224f501afdd8e9328b238000fd2f37bf30c03bcff14?s=96&d=mm&r=g\",\"contentUrl\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/e57206ca88c051844b618224f501afdd8e9328b238000fd2f37bf30c03bcff14?s=96&d=mm&r=g\",\"caption\":\"wpadmin\"},\"sameAs\":[\"http:\\\/\\\/wmtc2006.com\"],\"url\":\"https:\\\/\\\/wmtc2006.com\\\/?author=1\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4) - Discovery and characterization of Histamine-2 Receptor Antagonists","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/wmtc2006.com\/?p=950","og_locale":"en_US","og_type":"article","og_title":"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4) - Discovery and characterization of Histamine-2 Receptor Antagonists","og_description":"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4). Flow cytometry analysis was carried out using antibodies specific for CD4, CD8, TCR [...]","og_url":"https:\/\/wmtc2006.com\/?p=950","og_site_name":"Discovery and characterization of Histamine-2 Receptor Antagonists","article_published_time":"2026-03-08T14:59:34+00:00","author":"wpadmin","twitter_card":"summary_large_image","twitter_misc":{"Written by":"wpadmin","Est. reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/wmtc2006.com\/?p=950#article","isPartOf":{"@id":"https:\/\/wmtc2006.com\/?p=950"},"author":{"name":"wpadmin","@id":"http:\/\/wmtc2006.com\/#\/schema\/person\/5a1d916d8ed9c89b34ac45c96f81e776"},"headline":"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4)","datePublished":"2026-03-08T14:59:34+00:00","mainEntityOfPage":{"@id":"https:\/\/wmtc2006.com\/?p=950"},"wordCount":635,"articleSection":["Histamine Receptors"],"inLanguage":"en-US"},{"@type":"WebPage","@id":"https:\/\/wmtc2006.com\/?p=950","url":"https:\/\/wmtc2006.com\/?p=950","name":"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4) - Discovery and characterization of Histamine-2 Receptor Antagonists","isPartOf":{"@id":"http:\/\/wmtc2006.com\/#website"},"datePublished":"2026-03-08T14:59:34+00:00","author":{"@id":"http:\/\/wmtc2006.com\/#\/schema\/person\/5a1d916d8ed9c89b34ac45c96f81e776"},"breadcrumb":{"@id":"https:\/\/wmtc2006.com\/?p=950#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/wmtc2006.com\/?p=950"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/wmtc2006.com\/?p=950#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"http:\/\/wmtc2006.com\/"},{"@type":"ListItem","position":2,"name":"\ufeffTwo lines of transgenic founders were shown (line 1 and line 4)"}]},{"@type":"WebSite","@id":"http:\/\/wmtc2006.com\/#website","url":"http:\/\/wmtc2006.com\/","name":"Discovery and characterization of Histamine-2 Receptor Antagonists","description":"Just another WordPress site","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"http:\/\/wmtc2006.com\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Person","@id":"http:\/\/wmtc2006.com\/#\/schema\/person\/5a1d916d8ed9c89b34ac45c96f81e776","name":"wpadmin","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/secure.gravatar.com\/avatar\/e57206ca88c051844b618224f501afdd8e9328b238000fd2f37bf30c03bcff14?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/e57206ca88c051844b618224f501afdd8e9328b238000fd2f37bf30c03bcff14?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/e57206ca88c051844b618224f501afdd8e9328b238000fd2f37bf30c03bcff14?s=96&d=mm&r=g","caption":"wpadmin"},"sameAs":["http:\/\/wmtc2006.com"],"url":"https:\/\/wmtc2006.com\/?author=1"}]}},"_links":{"self":[{"href":"https:\/\/wmtc2006.com\/index.php?rest_route=\/wp\/v2\/posts\/950","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wmtc2006.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wmtc2006.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wmtc2006.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/wmtc2006.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=950"}],"version-history":[{"count":1,"href":"https:\/\/wmtc2006.com\/index.php?rest_route=\/wp\/v2\/posts\/950\/revisions"}],"predecessor-version":[{"id":951,"href":"https:\/\/wmtc2006.com\/index.php?rest_route=\/wp\/v2\/posts\/950\/revisions\/951"}],"wp:attachment":[{"href":"https:\/\/wmtc2006.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=950"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wmtc2006.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=950"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wmtc2006.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=950"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}