Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23.
The orphan receptor ChemR23 is a G-protein coupled receptor (GPCR) with homology to neuropeptide and chemoattractant receptors. Tazarotene, a synthetic retinoid activating retinoic acid receptor (RAR), up-regulates tazarotene-induced gene-2 (TIG2). The function and molecular target of this protein are now described. By means of reverse pharmacology screening using a peptide library generated from human hemofiltrate, we have isolated and identified TIG2 as the natural ligand of ChemR23 and report the specific molecular form of the bioactive, circulating TIG2, representing the amino-acid residues 21 to 154 of the 163 amino acid-containing prepropeptide. Based on the expression pattern of ChemR23 and TIG2, the physiological role in bone development, immune and inflammatory responses and the maintenance of skin is now being investigated.
Meder
W
W
IPF PharmaCeuticals GmbH, Feodor-Lynen-Str. 31, D-30625, Hannover, Germany. c.kutzleb@ipf-pharmaceuticals.de
Wendland
M
M
Busmann
A
A
Kutzleb
C
C
Spodsberg
N
N
John
H
H
Richter
R
R
Schleuder
D
D
Meyer
M
M
Forssmann
W G
WG
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D006224:Cricetinae; D005470:Fluorometry / Q000379:methods; D006440:Hemofiltration; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009539:Nicotinic Acids / Q000235:genetics*; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000097:blood* / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014162:Transfection; D012176:Retinoids
D002118:Calcium; D008024:Ligands; D009539:Nicotinic Acids; D010446:Peptide Fragments; D019707:Receptors, Chemokine; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; C102741:CMKLR1 protein, human; C086827:tazarotene; D012176:Retinoids