000292456 001__ 292456 000292456 005__ 20250514144601.0 000292456 0247_ $$2doi$$a10.1002/bies.202400144 000292456 0247_ $$2pmid$$apmid:39180250 000292456 0247_ $$2ISSN$$a0265-9247 000292456 0247_ $$2ISSN$$a1521-1878 000292456 0247_ $$2altmetric$$aaltmetric:167223247 000292456 037__ $$aDKFZ-2024-01723 000292456 041__ $$aEnglish 000292456 082__ $$a540 000292456 1001_ $$0P:(DE-He78)483ad6be7d7fe19e48db9cce86efd70e$$aNiehrs, Christof$$b0$$eFirst author$$udkfz 000292456 245__ $$aAn 'R-spondin code' for multimodal signaling ON-OFF states. 000292456 260__ $$aNew York, NY$$bWiley-Liss$$c2024 000292456 3367_ $$2DRIVER$$aarticle 000292456 3367_ $$2DataCite$$aOutput Types/Journal article 000292456 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1727677401_26754$$xReview Article 000292456 3367_ $$2BibTeX$$aARTICLE 000292456 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000292456 3367_ $$00$$2EndNote$$aJournal Article 000292456 500__ $$a#EA:A050#LA:A050# / DKFZ-ZMBH Alliance / 2024 Oct;46(10):e2400144 000292456 520__ $$aR-spondins (RSPOs) are a family of secreted proteins and stem cell growth factors that are potent co-activators of Wnt signaling. Recently, RSPO2 and RSPO3 were shown to be multifunctional, not only amplifying Wnt- but also binding BMP- and FGF receptors to downregulate signaling. The common mechanism underlying these diverse functions is that RSPO2 and RSPO3 act as 'endocytosers' that link transmembrane proteins to ZNRF3/RNF43 E3 ligases and trigger target internalization. Thus, RSPOs are natural protein targeting chimeras for cell surface proteins. Conducting data mining and cell surface binding assays we report additional candidate RSPO targets, including SMO, PTC1,2, LGI1, ROBO4, and PTPR(F/S). We propose that there is an 'R-spondin code' that imparts combinatorial signaling ON-OFF states of multiple growth factors. This code involves the modular RSPO domains, notably distinct motifs in the divergent RSPO-TSP1 domains to mediate target interaction and internalization. The RSPO code offers a novel framework for the understanding how diverse signaling pathways may be coordinately regulated in development and disease. 000292456 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0 000292456 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000292456 650_7 $$2Other$$aBMP 000292456 650_7 $$2Other$$aFGF 000292456 650_7 $$2Other$$aHedgehog 000292456 650_7 $$2Other$$aRāspondin 000292456 650_7 $$2Other$$aWnt 000292456 650_7 $$2Other$$aaxon guidance 000292456 650_7 $$2Other$$aphosphatases 000292456 650_7 $$2Other$$areceptor internalization 000292456 7001_ $$0P:(DE-He78)5b895ce811cc43507affc3795b4decab$$aSeidl, Carina$$b1 000292456 7001_ $$0P:(DE-He78)b2253633681399146975628b760ff3e0$$aLee, Hyeyoon$$b2$$eLast author$$udkfz 000292456 773__ $$0PERI:(DE-600)1473795-4$$a10.1002/bies.202400144$$gp. 2400144$$n10$$pe2400144$$tBioessays$$v46$$x0265-9247$$y2024 000292456 8564_ $$uhttps://inrepo02.dkfz.de/record/292456/files/BioEssays%20-%202024%20-%20Niehrs%20-%20An%20R%E2%80%90spondin%20code%20for%20multimodal%20signaling%20ON%E2%80%90OFF%20states.pdf 000292456 8564_ $$uhttps://inrepo02.dkfz.de/record/292456/files/BioEssays%20-%202024%20-%20Niehrs%20-%20An%20R%E2%80%90spondin%20code%20for%20multimodal%20signaling%20ON%E2%80%90OFF%20states.pdf?subformat=pdfa$$xpdfa 000292456 909CO $$ooai:inrepo02.dkfz.de:292456$$pVDB 000292456 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)483ad6be7d7fe19e48db9cce86efd70e$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000292456 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)5b895ce811cc43507affc3795b4decab$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000292456 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)b2253633681399146975628b760ff3e0$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ 000292456 9131_ $$0G:(DE-HGF)POF4-311$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vZellbiologie und Tumorbiologie$$x0 000292456 9141_ $$y2024 000292456 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2023-08-28$$wger 000292456 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2023-08-28$$wger 000292456 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)1120$$2StatID$$aDBCoverage$$bBIOSIS Reviews Reports And Meetings$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBIOESSAYS : 2022$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-08-28 000292456 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2023-08-28 000292456 9202_ $$0I:(DE-He78)A050-20160331$$kA050$$lA050 Molekulare Embryologie$$x0 000292456 9201_ $$0I:(DE-He78)A050-20160331$$kA050$$lA050 Molekulare Embryologie$$x0 000292456 9200_ $$0I:(DE-He78)A050-20160331$$kA050$$lA050 Molekulare Embryologie$$x0 000292456 980__ $$ajournal 000292456 980__ $$aVDB 000292456 980__ $$aI:(DE-He78)A050-20160331 000292456 980__ $$aUNRESTRICTED