Tissue restricted expression of two human Frzbs in preadipocytes and pancreas.
Frzb is a newly discovered family of secreted glycoproteins that function to modulate signaling activity of Wnt. Frzb proteins share sequence homology with the extracellular domain of the Wnt receptor (frizzled) and are capable of binding to Wnt. Thus, Frzb functions to antagonize Wnt activity by sequestering Wnt and preventing its binding to the frizzled receptor. Since the initial identification of bovine and human Frzb, several related members of this family have been isolated from rodent and human. In this paper, we describe the cloning and expression of two human frzb homologues termed hFRP-1b and hFRP-2. These human FRPs share significant homology to mouse sFRP-1 and sFRP-2 (55 and 98% identity at amino acid level, respectively). Northern blot experiments revealed that these Frzb homologues have highly restricted tissue distribution. hFRP-1b is exclusively expressed in pancreatic tissue while high levels of hFRP-2 were found in adipose tissue. In addition, low levels of hFRP-2 were also observed in other tissues including heart, pancreas and muscle. Remarkably, FRP-2 is predominantly expressed in un-differentiated preadipocytes in both rodent and man. The expression of FRP-2 is also significantly reduced in fat pads from obese mice. Taken together, these data indicate that distinctive members of the Frzb family exhibit different expression patterns in vivo, suggesting their ability to modulate diverse aspects of Wnt signaling. The expression and dysregulation of sFRP-2 in fat and obesity also suggest a potential roles on the Wnt signaling pathway in the pathology of obesity and related metabolic diseases. Molecular cloning and expression of these Frzbs will allow detailed molecular and biochemical analysis of Wnt-Frzb interaction and their impact on Wnt-Frizzled receptor signal transduction.
Hu
E
E
Department of Renal Pharmacology, Department of Bio-Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, Pennsylvania, 19406, USA.
Zhu
Y
Y
Fredrickson
T
T
Barnes
M
M
Kelsell
D
D
Beeley
L
L
Brooks
D
D
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D051157:Frizzled Receptors; D015870:Gene Expression; D006023:Glycoproteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D014018:Tissue Distribution; D000099274:Frizzled-Related Proteins
D018076:DNA, Complementary; D051157:Frizzled Receptors; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D000099274:Frizzled-Related Proteins