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J. Biol. Chem., Vol. 277, Issue 2, 1148-1157, January 11, 2002
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From the Howard Florey Institute of Experimental Physiology and
Medicine, University of Melbourne, Victoria 3010 and the
¶ Department of Pharmacology, Monash University, Clayton,
Victoria 3800, Australia
We have identified a novel human relaxin gene,
designated H3 relaxin, and an equivalent relaxin
gene in the mouse from the Celera Genomics data base. Both genes encode
a putative prohormone sequence incorporating the classic two-chain,
three cysteine-bonded structure of the relaxin/insulin family and,
importantly, contain the RXXXRXX(I/V) motif in
the B-chain that is essential for relaxin receptor binding. A peptide
derived from the likely proteolytic processing of the H3 relaxin
prohormone sequence was synthesized and found to possess relaxin
activity in bioassays utilizing the human monocytic cell line, THP-1,
that expresses the relaxin receptor. The expression of this
novel relaxin gene was studied in mouse tissues using RT-PCR, where
transcripts were identified with a pattern of expression distinct from
that of the previously characterized mouse relaxin. The highest levels
of expression were found in the brain, whereas significant expression
was also observed in the spleen, thymus, lung, and ovary. Northern
blotting demonstrated an ~1.2-kb transcript present in mouse brain
poly(A) RNA but not in other tissues. These data, together with the
localization of transcripts in the pars ventromedialis of the dorsal
tegmental nucleus of C57BLK6J mouse brain by in situ
hybridization histochemistry, suggest a new role for relaxin in
neuropeptide signaling processes. Together, these studies describe a
third member of the human relaxin family and its equivalent in the mouse.
Human Relaxin Gene 3 (H3) and the Equivalent Mouse
Relaxin (M3) Gene
NOVEL MEMBERS OF THE RELAXIN PEPTIDE FAMILY*
,
,
*
This work was supported in part by a block grant to the
Howard Florey Institute (Reg Key 983001) from the National Health and
Medical Research Council of Australia.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of an Australian Research Council QEII fellowship.
Recipient of a National Health and Medical Research Council
of Australia R. D. Wright fellowship. To whom correspondence
should be addressed. Tel.: 61-3-8344-5648; Fax: 61-3-9348-1707;
E-mail: r.bathgate@hfi.unimelb.edu.au.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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