A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors.
This paper describes the identification of a new family of mammalian genes that encode secreted proteins containing homology to the cysteine-rich ligand-binding domain found in the frizzled family of transmembrane receptors. The secreted frizzled-related proteins (sFRPs) are approximately 30 kDa in size, and each contains a putative signal sequence, a frizzled-like cysteine-rich domain, and a conserved hydrophilic carboxy-terminal domain. The sFRPs are not the products of differential splicing of the known frizzled genes. Glycosylphosphatidylinositol-anchored derivatives of sFRP-2 and sFRP-3 produced in transfected human embryonic kidney cells confer cell-surface binding by the Drosophila Wingless protein. These observations suggest that sFRPs may function in vivo to modulate Wnt signaling, or, alternatively, as novel ligands for as yet unidentified receptors.
Rattner
A
A
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hsieh
J C
JC
Smallwood
P M
PM
Gilbert
D J
DJ
Copeland
N G
NG
Jenkins
N A
NA
Nathans
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D018076:DNA, Complementary; D029721:Drosophila Proteins; D005260:Female; D051157:Frizzled Receptors; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D017386:Sequence Homology, Amino Acid; D051155:Wnt1 Protein
D018076:DNA, Complementary; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D051155:Wnt1 Protein; C058784:fz protein, Drosophila; C074622:wg protein, Drosophila