{"id":923,"date":"2015-01-16T10:31:50","date_gmt":"2015-01-16T01:31:50","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=923"},"modified":"2015-01-16T10:31:50","modified_gmt":"2015-01-16T01:31:50","slug":"journal-club-2015-1-16","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=923","title":{"rendered":"Journal Club 2015.1.16"},"content":{"rendered":"<h1><div class=\"attachments\"><dl class=\"attachments attachments-medium\">\r\n<dt class=\"icon\">\r\n\t<a title=\"Cathepsin S signals via PAR2 and generates a novel tethered ligand receptor agonist\" href=\"https:\/\/misterx95.myds.me\/wordpress\/?p=923&aid=926&sa=0\" >\r\n\t\t<img src=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/plugins\/eg-attachments\/img\/flags\/document.png\" width=\"32\" height=\"32\"  alt=\"Cathepsin S signals via PAR2 and generates a novel tethered ligand receptor agonist\" \/>\r\n\t<\/a>\r\n<\/dt>\r\n<dd class=\"caption\">\r\n\t<strong>Filename<\/strong> : <a title=\"Cathepsin S signals via PAR2 and generates a novel tethered ligand receptor agonist\" href=\"https:\/\/misterx95.myds.me\/wordpress\/?p=923&aid=926&sa=0\" >cathepsin-s-signals-via-par2-and-generates-a-novel-tethered-ligand-receptor-agonist.pdf<\/a> (789 KB)\r\n\t<br>\r\n\t<strong>Caption<\/strong> : \r\n<\/dd>\r\n<\/dl><p><\/p><\/div><\/h1>\n<h1><span class=\"highlight\">Cathepsin<\/span> <span class=\"highlight\">S<\/span> <span class=\"highlight\">signals<\/span> <span class=\"highlight\">via<\/span> <span class=\"highlight\">PAR2<\/span> and <span class=\"highlight\">generates<\/span> a <span class=\"highlight\">novel<\/span> <span class=\"highlight\">tethered<\/span> <span class=\"highlight\">ligand<\/span> <span class=\"highlight\">receptor<\/span> <span class=\"highlight\">agonist<\/span>.<\/h1>\n<div class=\"auths\"><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Elmariah%20SB%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=24964046\">Elmariah SB<\/a><sup>1<\/sup>, <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Reddy%20VB%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=24964046\">Reddy VB<\/a><sup>1<\/sup>, <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Lerner%20EA%5BAuthor%5D&amp;cauthor=true&amp;cauthor_uid=24964046\">Lerner EA<\/a><sup>1<\/sup>.<\/div>\n<div class=\"afflist\">\n<h3><a class=\"jig-ncbitoggler ui-widget ui-ncbitoggler\" title=\"Open\/close author information list\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Cathepsin%20S%20Signals%20via%20PAR2%20and%20Generates%20a%20Novel%20Tethered%20Ligand%20Receptor%20Agonist#\"><span class=\"ui-ncbitoggler-master-text\">Author information<\/span><\/a><\/h3>\n<div class=\"ui-helper-reset\"><\/div>\n<\/div>\n<div class=\"abstr\">\n<h3>Abstract<\/h3>\n<div class=\"\">\n<p>Protease-activated <span class=\"highlight\">receptor<\/span>-2 is widely expressed in mammalian epithelial, immune and neural tissues. Cleavage of <span class=\"highlight\">PAR2<\/span> by serine proteases leads to self-activation of the <span class=\"highlight\">receptor<\/span> by the <span class=\"highlight\">tethered<\/span> <span class=\"highlight\">ligand<\/span> SLIGRL. The contribution of other classes of proteases to PAR activation has not been studied in detail. <span class=\"highlight\">Cathepsin<\/span> <span class=\"highlight\">S<\/span> is a widely expressed cysteine protease that is upregulated in inflammatory conditions. It has been suggested that<span class=\"highlight\">cathepsin<\/span> <span class=\"highlight\">S<\/span> activates <span class=\"highlight\">PAR2<\/span>. However, <span class=\"highlight\">cathepsin<\/span> <span class=\"highlight\">S<\/span> activation of <span class=\"highlight\">PAR2<\/span> has not been demonstrated directly nor has the potential mechanism of activation been identified. We show that <span class=\"highlight\">cathepsin<\/span> <span class=\"highlight\">S<\/span> cleaves near the N-terminus of <span class=\"highlight\">PAR2<\/span> to expose a <span class=\"highlight\">novel<\/span> <span class=\"highlight\">tethered<\/span> <span class=\"highlight\">ligand<\/span>, KVDGTS. The hexapeptide KVDGTS <span class=\"highlight\">generates<\/span> downstream signaling events specific to <span class=\"highlight\">PAR2<\/span> but is weaker than SLIGRL. Mutation of the <span class=\"highlight\">cathepsin<\/span> <span class=\"highlight\">S<\/span> cleavage site prevents <span class=\"highlight\">receptor<\/span> activation by the protease while KVDGTS retains activity. In conclusion, the range of actions previously ascribed to cysteine cathepsins in general, and <span class=\"highlight\">cathepsin<\/span> <span class=\"highlight\">S<\/span> in particular, should be expanded to include molecular signaling. Such signaling may link together observations that had been attributed previously to <span class=\"highlight\">PAR2<\/span> or <span class=\"highlight\">cathepsin<\/span> <span class=\"highlight\">S<\/span> individually. These interactions may contribute to inflammation.<\/p>\n<\/div>\n<\/div>\n<div class=\"aux\"><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Cathepsin S signals via PAR2 and generates a novel tethered ligand receptor agonist. Elmariah SB1, Reddy VB1, Lerner EA1. Author information Abstract Protease-activated receptor-2 is widely expressed in mammalian epithelial, immune and neural tissues. Cleavage of PAR2 by serine proteases leads to self-activation of the receptor by the tethered ligand SLIGRL. The contribution of other [&hellip;]<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/923"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=923"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/923\/revisions"}],"predecessor-version":[{"id":928,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/923\/revisions\/928"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=923"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=923"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=923"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}