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RXFP1 Couples to the Gα i3 ‐Gβγ‐PI3K‐PKCζ Pathway via the Final 10 Amino Acids of the Receptor C‐terminal Tail
Author(s) -
Halls Michelle L.,
Papaioannou Maria,
Wade John D.,
Evans Bronwyn A.,
Bathgate Ross A. D.,
Summers Roger J.
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2008.03813.x
Subject(s) - relaxin , receptor , g protein coupled receptor , microbiology and biotechnology , enzyme linked receptor , chemistry , signal transduction , amino acid , g protein , 5 ht5a receptor , biochemistry , biology
The relaxin family peptide receptors RXFP1 and RXFP2 are highly similar receptors that share approximately 80% amino acid sequence homology. Constitutively active receptors couple to increased cAMP accumulation, which is important for relaxin‐mediated decidualization and myometrial inhibition. Despite the high homology, the receptors couple to different G‐proteins to affect cAMP accumulation. This study aimed to determine the region of RXFP1 that directs coupling to the delayed Gα i3 pathway by using receptor mutagenesis. Receptor chimeras suggested that activation of this pathway by RXFP1 was dependent upon the membrane‐anchored domain of the receptor. Further receptor mutagenesis showed that activation of the Gα i3 ‐Gβγ‐PI3K‐PKCζ cAMP pathway by RXFP1 is dependent upon the C‐terminal 10 amino acids of the receptor and absolutely requires Arg 752 .