The biochemical properties and transforming potential of human Wnt-2 are similar to Wnt-1.
Wnt-2 is a member of the Wnt gene family that includes the proto-oncogene Wnt-1 (formerly Int-1). Although the predicted protein product of the Wnt-2 gene has only 38% amino acid identity with Wnt-1, it exhibits significant conservation of structural properties, including a hydrophobic signal sequence and invariant spacing and conservation of 22 cysteine residues. We have sought to characterize the biological and biochemical properties of Wnt family members and here present a characterization of Wnt-2 protein and a comparison with Wnt-1. We demonstrate, using both CHO and AtT-20 cells transfected with human Wnt-2 cDNA, that Wnt-2 encodes a 33 kDa protein that is modified by N-linked glycosylation to a 35 kDa species. Secreted Wnt-2 protein was detected in the culture medium only after cells were treated with suramin indicating that, like Wnt-1 protein, Wnt-2 is tightly associated with the cell surface. Expression of Wnt-2 cDNA in the mammary epithelial cell line C57 mg results in loss of density-inhibited growth and induces a transformed phenotype in monolayer culture similar to the effects produced by Wnt-1. These results indicate that Wnt-2 shares several biochemical and biological characteristics with Wnt-1 and suggests that other Wnt family members, by virtue of conserved structural features, may also exhibit similar properties.
Syntex Research, Palo Alto, California 94304.
A
A
Blasband
B
B
Schryver
J
J
Papkoff
D000818:Animals; D016466:CHO Cells; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006224:Cricetinae; D006031:Glycosylation; D006801:Humans; D008970:Molecular Weight; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D011519:Proto-Oncogenes; D012313:RNA / Q000032:analysis*; D014162:Transfection; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051154:Wnt2 Protein; D029961:Zebrafish Proteins
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C495247:WNT1 protein, human; C495244:WNT2 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051154:Wnt2 Protein; D029961:Zebrafish Proteins; D012313:RNA