Details

Autor(en) / Beteiligte

• Svendsen, Angela Manegold
• Vrecl, Milka
• Ellis, Tina M
• Heding, Anders
• Kristensen, Jesper Bøggild
• Wade, John D
• Bathgate, Ross A. D
• De Meyts, Pierre
• Nøhr, Jane

Titel

Cooperative Binding of Insulin-Like Peptide 3 to a Dimeric Relaxin Family Peptide Receptor 2

Ist Teil von

• Endocrinology (Philadelphia), 2008-03, Vol.149 (3), p.1113-1120

Ort / Verlag

Bethesda, MD: Endocrine Society

Erscheinungsjahr

2008

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Insulin-like peptide 3 (INSL3) binds to a G protein-coupled receptor (GPCR) called relaxin family peptide receptor 2 (RXFP2). RXFP2 belongs to the leucine-rich repeat-containing subgroup (LGR) of class A GPCRs. Negative cooperativity has recently been demonstrated in other members of the LGR subgroup. In this work, the kinetics of INSL3 binding to HEK293 cells stably transfected with RXFP2 (HEK293-RXFP2) have been investigated in detail to study whether negative cooperativity occurs and whether this receptor functions as a dimer. Our results show that negative cooperativity is present and that INSL3-RXFP2 binding shows both similarities and differences with insulin binding to the insulin receptor. A dose-response curve for the negative cooperativity of INSL3 binding had a reverse bell shape reminiscent of that seen for the negative cooperativity of insulin binding to its receptor. This suggests that binding of INSL3 may happen in a trans rather than in a cis way in a receptor dimer. Bioluminescence resonance energy transfer (BRET2) experiments confirmed that RXFP2 forms constitutive homodimers. Heterodimerization between RXFP2 and RXFP1 was also observed.