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Volume 271, Number 44,
Issue of November 1, 1996
pp. 27776-27781
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Molecular Characterization of a Second Mouse Pancreatic
Polypeptide Receptor and Its Inactivated Human Homologue
(Received for publication, June 28, 1996)
Paul
Gregor
,
Yun
Feng
,
Lynn B.
DeCarr
,
Linda J.
Cornfield
and
Michael L.
McCaleb
From the Metabolic Disorders Research, Bayer Corporation, West
Haven, Connecticut 06516
The family of mammalian neuropeptide Y
(NPY)/peptide YY (PYY)/pancreatic polypeptide (PP) receptors comprises
several G protein-coupled receptors, i.e. Y1, Y2, and
Y4/PP1. We now report cloning of a novel member of this family named
PP2. The coding region of the mouse PP2 gene reveals no
introns and predicts a seven transmembrane domain (TM) receptor of 371 amino acids. Percent identities of the mouse PP2 to mouse Y1, mouse
Y4/PP1 and human Y2 receptors are 53, 42, and 31, respectively. The
mouse PP2 receptor expressed in COS cells binds rat 125I-PP
with high affinity, i.e. IC50 = 65 pM. Pharmacological characterization of 125I-PP
binding shows a rank order of potency of PP PYY NPY,
which is similar to that of the mouse Y4/PP1 receptor. Mouse PP2
transcripts were not detectable by Northern analysis in adult tissues
and in 11-, 15-, and 17-day-old embryos. However, a 9.8-kb PP2
transcript was detectable in 7-day-old mouse embryo, i.e.
prior to the organogenesis of pancreas and the onset of PP production.
We have also cloned the human homologue of PP2, which is a
single copy gene and maps to human chromosome 5q31. Surprisingly, the
human PP2 cDNAs and gene sequences display a single
base deletion in the coding region. This frameshifting mutation
predicts a truncated receptor of 290 amino acids without TM7.
Transfection of COS-7 cells with several different human PP2 expression
constructs failed to confirm any specific binding of
125I-PP, 125I-PYY, or 125I-NPY to
cell membranes. These data suggest that in mouse there are at least two
PP receptors, Y4/PP1 and PP2, whereas in humans, PP2 is either
functionally inactive or it has acquired a PP-independent function.

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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
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