FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386446287> ?p ?o ?g. }

• W4386446287 abstract "Abstract Growth hormone (GH) receptor (GHR) and prolactin (PRL) receptor (PRLR) are transmembrane class I cytokine receptors that co-exist in various normal and cancerous cells. Both receptors respond to their associated ligands predominantly by activating the Janus Kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) signaling pathways, and both are also known to initiate receptor-specific JAK2-independent signaling. Together with their cognate ligands, these receptors have been associated with pro-tumorigenic effects in various cancers, including breast cancer (BC). Human GH is known to bind GHR and PRLR, while PRL can only bind PRLR. A growing body of work suggests that GHR and PRLR can form heteromers in BC cells, modulating GH signal transduction. However, the dynamics of PRLR and GHR on the plasma membrane and how these could affect their respective signaling still need to be understood. To this end, we set out to unravel the spatiotemporal dynamics of GHR and PRLR on the surface of human T47D breast cancer cells and γ2A-JAK2 cells. We applied direct stochastic optical reconstruction microscopy (dSTORM) and quantified the colocalization and availability of both receptors on the plasma membrane at the nanometer scale at different time points following treatment with GH and PRL. In cells co-expressing GHR and PRLR, we surprisingly observed that not only GH but also PRL treatment induces a significant loss of surface GHR. In cells lacking PRLR or expressing a mutant PRLR deficient in JAK2 binding, we observed that GH induces downregulation of membrane-bound GHR, but PRL no longer induces loss of surface GHR. Colocalizations of GHR and PRLR were confirmed by proximity ligation (PL) assay. Our results suggest that PRLR-GHR interaction, direct or indirect, is indispensable for PRL-but not GH-induced loss of surface GHR and for both GH-induced and PRL-induced increase of surface PRLR, with potential consequences for downstream signaling. Furthermore, our results suggest that JAK2 binding via the receptor intracellular domain’s Box1 element is crucial for the observed regulation of one class I cytokine receptor’s cell surface availability via ligand-induced activation of another class I cytokine receptor. Our findings shed new light on the reciprocal and collective role that PRLR and GHR play in regulating cell signaling." @default.
• W4386446287 created "2023-09-06" @default.
• W4386446287 creator A5009647225 @default.
• W4386446287 creator A5016995908 @default.
• W4386446287 creator A5028880384 @default.
• W4386446287 creator A5042438246 @default.
• W4386446287 creator A5058815495 @default.
• W4386446287 creator A5063253432 @default.
• W4386446287 date "2023-09-05" @default.
• W4386446287 modified "2023-09-27" @default.
• W4386446287 title "A role for JAK2 in mediating cell surface GHR-PRLR interaction" @default.
• W4386446287 cites W14299924 @default.
• W4386446287 cites W1529354907 @default.
• W4386446287 cites W1973396607 @default.
• W4386446287 cites W1976450316 @default.
• W4386446287 cites W1976830810 @default.
• W4386446287 cites W1977107368 @default.
• W4386446287 cites W1982685226 @default.
• W4386446287 cites W1985832876 @default.
• W4386446287 cites W1988136888 @default.
• W4386446287 cites W1990431872 @default.
• W4386446287 cites W1992023050 @default.
• W4386446287 cites W1992452530 @default.
• W4386446287 cites W2001022761 @default.
• W4386446287 cites W2011675507 @default.
• W4386446287 cites W2027700316 @default.
• W4386446287 cites W2029769116 @default.
• W4386446287 cites W2040160058 @default.
• W4386446287 cites W2057710811 @default.
• W4386446287 cites W2059407087 @default.
• W4386446287 cites W2061842937 @default.
• W4386446287 cites W2068187158 @default.
• W4386446287 cites W2081178923 @default.
• W4386446287 cites W2086201614 @default.
• W4386446287 cites W2094112482 @default.
• W4386446287 cites W2099209030 @default.
• W4386446287 cites W2109066322 @default.
• W4386446287 cites W2116584173 @default.
• W4386446287 cites W2120166425 @default.
• W4386446287 cites W2122628672 @default.
• W4386446287 cites W2123056334 @default.
• W4386446287 cites W2127327838 @default.
• W4386446287 cites W2136692995 @default.
• W4386446287 cites W2139960040 @default.
• W4386446287 cites W2146864318 @default.
• W4386446287 cites W2156578747 @default.
• W4386446287 cites W2158189264 @default.
• W4386446287 cites W2158602749 @default.
• W4386446287 cites W2158951069 @default.
• W4386446287 cites W2172032243 @default.
• W4386446287 cites W2301343927 @default.
• W4386446287 cites W2303912398 @default.
• W4386446287 cites W2325314951 @default.
• W4386446287 cites W2339358819 @default.
• W4386446287 cites W2360712610 @default.
• W4386446287 cites W2484544705 @default.
• W4386446287 cites W2518602358 @default.
• W4386446287 cites W2521913548 @default.
• W4386446287 cites W2591939515 @default.
• W4386446287 cites W2604536255 @default.
• W4386446287 cites W2616928992 @default.
• W4386446287 cites W2740679065 @default.
• W4386446287 cites W2765381479 @default.
• W4386446287 cites W2885018212 @default.
• W4386446287 cites W2902301880 @default.
• W4386446287 cites W2946013369 @default.
• W4386446287 cites W2968994994 @default.
• W4386446287 cites W3005420401 @default.
• W4386446287 cites W3008170628 @default.
• W4386446287 cites W3080296032 @default.
• W4386446287 cites W3083889121 @default.
• W4386446287 cites W3098957206 @default.
• W4386446287 cites W3104756028 @default.
• W4386446287 cites W3110461670 @default.
• W4386446287 cites W3175881592 @default.
• W4386446287 cites W3199298281 @default.
• W4386446287 cites W4205992865 @default.
• W4386446287 cites W4233056538 @default.
• W4386446287 cites W4282976740 @default.
• W4386446287 cites W4283314599 @default.
• W4386446287 cites W4289704726 @default.
• W4386446287 cites W4311884363 @default.
• W4386446287 doi "https://doi.org/10.1101/2023.09.01.555812" @default.
• W4386446287 hasPublicationYear "2023" @default.
• W4386446287 type Work @default.
• W4386446287 citedByCount "0" @default.
• W4386446287 crossrefType "posted-content" @default.
• W4386446287 hasAuthorship W4386446287A5009647225 @default.
• W4386446287 hasAuthorship W4386446287A5016995908 @default.
• W4386446287 hasAuthorship W4386446287A5028880384 @default.
• W4386446287 hasAuthorship W4386446287A5042438246 @default.
• W4386446287 hasAuthorship W4386446287A5058815495 @default.
• W4386446287 hasAuthorship W4386446287A5063253432 @default.
• W4386446287 hasBestOaLocation W43864462871 @default.
• W4386446287 hasConcept C112392421 @default.
• W4386446287 hasConcept C113675107 @default.
• W4386446287 hasConcept C126322002 @default.
• W4386446287 hasConcept C134018914 @default.
• W4386446287 hasConcept C170493617 @default.
• W4386446287 hasConcept C171958077 @default.

• next