Lymphoguanylin: cloning and characterization of a unique member of the guanylin peptide family.
Guanylin and uroguanylin are small peptides containing two disulfide bonds that activate membrane guanylate cyclase-receptors in the intestine, kidney and other epithelia. Hybridization assays with a uroguanylin complementary DNA (cDNA) detected uroguanylin-like messenger RNAs (mRNAs) in the opossum spleen and testis, but these transcripts are larger than uroguanylin mRNAs. RT of RNA from spleen to produce cDNAs for amplification in the PCR followed by cloning and sequencing revealed a novel lymphoid-derived cDNA containing an open reading frame encoding a 109-amino acid polypeptide. This protein shares 84% and 40% of its residues with preprouroguanylin and preproguanylin, respectively. A 15-amino acid, uroguanylin-like peptide occurs at the COOH-terminus of the precursor polypeptide. However, this peptide is unique in having only three cysteine residues. We named the gene and its peptide product lymphoguanylin because the source of the first cDNA isolated was spleen and its mRNA is expressed in all of the lymphoid tissues tested. A 15-amino acid form of lymphoguanylin containing a single disulfide bond was synthesized that activates the guanylate cyclase receptors of human T84 intestinal and opossum kidney (OK) cells, although with less potency than uroguanylin and guanylin. Northern and/or RT-PCR assays detected lymphoguanylin mRNA transcripts in many tissues and organs of opossums, including those within the lymphoid/immune, cardiovascular/renal, reproductive, and central nervous organ systems. Lymphoguanylin joins guanylin and uroguanylin in a growing family of peptide agonists that activate transmembrane guanylate cyclase receptors, thus influencing target cell function via the intracellular second messenger, cGMP.
Forte
L R
LR
Harry S. Truman Memorial Veterans' Hospital, Department of Pharmacology, School of Medicine, Missouri University, Columbia 65212, USA. lrf@missouri.edu
Eber
S L
SL
Fan
X
X
London
R M
RM
Wang
Y
Y
Rowland
L M
LM
Chin
D T
DT
Freeman
R H
RH
Krause
W J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006152:Cyclic GMP / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry; D005768:Gastrointestinal Hormones; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008221:Lymphoid Tissue / Q000737:chemistry; D008297:Male; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides; D009893:Opossums / Q000235:genetics*; D009928:Organ Specificity; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017385:Sequence Homology; D013154:Spleen / Q000737:chemistry; D013737:Testis / Q000737:chemistry
D018076:DNA, Complementary; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; D012333:RNA, Messenger; C118275:lymphoguanylin; C072685:guanylin; C084362:uroguanylin; D006152:Cyclic GMP