A new secreted protein that binds to Wnt proteins and inhibits their activities.
The Wnt proteins constitute a large family of extracellular signalling molecules that are found throughout the animal kingdom and are important for a wide variety of normal and pathological developmental processes. Here we describe Wnt-inhibitory factor-1 (WIF-1), a secreted protein that binds to Wnt proteins and inhibits their activities. WIF-1 is present in fish, amphibia and mammals, and is expressed during Xenopus and zebrafish development in a complex pattern that includes paraxial presomitic mesoderm, notochord, branchial arches and neural crest derivatives. We use Xenopus embryos to show that WIF-1 overexpression affects somitogenesis (the generation of trunk mesoderm segments), in agreement with its normal expression in paraxial mesoderm. In vitro, WIF-1 binds to Drosophila Wingless and Xenopus Wnt8 produced by Drosophila S2 cells. Together with earlier results obtained with the secreted Frizzled-related proteins, our results indicate that Wnt proteins interact with structurally diverse extracellular inhibitors, presumably to fine-tune the spatial and temporal patterns of Wnt activity.
Hsieh
J C
JC
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kodjabachian
L
L
Rebbert
M L
ML
Rattner
A
A
Smallwood
P M
PM
Samos
C H
CH
Nusse
R
R
Dawid
I B
IB
Nathans
J
J
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006224:Cricetinae; D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051153:Wnt Proteins; D051155:Wnt1 Protein; D014981:Xenopus; D029867:Xenopus Proteins; D015027:Zebrafish; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C485569:WIF1 protein, human; C118544:Wif1 protein, mouse; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C074622:wg protein, Drosophila; C495248:wnt8a protein, Xenopus; C094522:wnt8b protein, zebrafish