Your browser doesn't support javascript.
loading
Activation of Adhesion G Protein-coupled Receptors: AGONIST SPECIFICITY OF STACHEL SEQUENCE-DERIVED PEPTIDES.
Demberg, Lilian M; Winkler, Jana; Wilde, Caroline; Simon, Kay-Uwe; Schön, Julia; Rothemund, Sven; Schöneberg, Torsten; Prömel, Simone; Liebscher, Ines.
Afiliación
  • Demberg LM; From the Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry and.
  • Winkler J; From the Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry and.
  • Wilde C; From the Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry and.
  • Simon KU; From the Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry and.
  • Schön J; From the Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry and.
  • Rothemund S; the Core Unit Peptide Technologies, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
  • Schöneberg T; From the Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry and.
  • Prömel S; From the Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry and simone.proemel@medizin.uni-leipzig.de.
  • Liebscher I; From the Rudolf Schönheimer Institute of Biochemistry, Molecular Biochemistry and ines.liebscher@medizin.uni-leipzig.de.
J Biol Chem ; 292(11): 4383-4394, 2017 03 17.
Article en En | MEDLINE | ID: mdl-28154189
Members of the adhesion G protein-coupled receptor (aGPCR) family carry an agonistic sequence within their large ectodomains. Peptides derived from this region, called the Stachel sequence, can activate the respective receptor. As the conserved core region of the Stachel sequence is highly similar between aGPCRs, the agonist specificity of Stachel sequence-derived peptides was tested between family members using cell culture-based second messenger assays. Stachel peptides derived from aGPCRs of subfamily VI (GPR110/ADGRF1, GPR116/ADGRF5) and subfamily VIII (GPR64/ADGRG2, GPR126/ADGRG6) are able to activate more than one member of the respective subfamily supporting their evolutionary relationship and defining them as pharmacological receptor subtypes. Extended functional analyses of the Stachel sequences and derived peptides revealed agonist promiscuity, not only within, but also between aGPCR subfamilies. For example, the Stachel-derived peptide of GPR110 (subfamily VI) can activate GPR64 and GPR126 (both subfamily VIII). Our results indicate that key residues in the Stachel sequence are very similar between aGPCRs allowing for agonist promiscuity of several Stachel-derived peptides. Therefore, aGPCRs appear to be pharmacologically more closely related than previously thought. Our findings have direct implications for many aGPCR studies, as potential functional overlap has to be considered for in vitro and in vivo studies. However, it also offers the possibility of a broader use of more potent peptides when the original Stachel sequence is less effective.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Receptores Acoplados a Proteínas G Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Receptores Acoplados a Proteínas G Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos