{"id":6360,"date":"2023-02-17T06:48:53","date_gmt":"2023-02-17T06:48:53","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2019-the-n-termini-of-grk2-and-grk3-simulate-the-stimulating-effects-of-rkip-on-%ce%b2-adrenoceptors\/"},"modified":"2023-02-17T06:48:53","modified_gmt":"2023-02-17T06:48:53","slug":"2019-the-n-termini-of-grk2-and-grk3-simulate-the-stimulating-effects-of-rkip-on-%ce%b2-adrenoceptors","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2019-the-n-termini-of-grk2-and-grk3-simulate-the-stimulating-effects-of-rkip-on-%ce%b2-adrenoceptors\/","title":{"rendered":"2019 &#8211; The N-termini of GRK2 and GRK3 simulate the stimulating effects of RKIP on \u03b2-adrenoceptors"},"content":{"rendered":"<p>The Raf kinase inhibitor protein (RKIP) activates \u03b2-adrenoceptors (\u03b2-AR) and thereby induces a well-tolerated cardiac contractility and prevents heart failure in mice. Different to RKIP-mediated \u03b2-AR activation, chronic activation of \u03b2-AR by catecholamines was shown to be detrimental for the heart. RKIP is an endogenous inhibitor of G protein coupled receptor kinase 2 (GRK2); it binds GRK2 and thereby inhibits GRK2 mediated \u03b2-AR phosphorylation and desensitization. Here, we evaluate RKIP-mediated effects on \u03b2-AR to explore new strategies for \u03b2-AR modulation. Co-immunoprecipitation assays and pull-down assays revealed subtype specificity of RKIP for the cardiac GRK isoforms GRK2 and GRK3 \u2013 not GRK5 \u2013 as well as several RKIP binding sites within their N-termini (GRK21\u2212185\u00a0and GRK31\u2212185). Overexpression of these N-termini prevented \u03b22-AR phosphorylation and internalization, subsequently increased receptor signaling in HEK293\u202fcells and cardiomyocyte contractility. Co-immunoprecipitation assays of \u03b22-AR with these N-terminal GRK fragments revealed a direct interaction suggesting a steric interference of the fragments with the functional GRK-receptor interaction. Altogether, N-termini of GRK2 and GRK3 efficiently simulate RKIP effects on \u03b2-AR signaling in HEK293\u202fcells and in cardiomyocytes by their binding to \u03b22-AR and, thus, provide important insights for the development of new strategies to modulate \u03b22-AR signaling.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[77],"therapeutic_areas":[54],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-6360","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6360","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6360"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6360"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6360"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6360"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6360"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6360"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6360"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6360"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6360"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}