PROSITE documentation PDOC00219

Wnt-1 family signature

Wnt-1 (previously known as int-1) [1] is a proto-oncogene induced by the integration of the mouse mammary tumor virus. It is thought to play a role in intercellular communication and seems to be a signalling molecule important in the development of the central nervous system (CNS). The sequence of wnt-1 is highly conserved in mammals, fish, and amphibians.

Wnt-1 is a member of a large family of related proteins [2,3,4] that are all thought to be developmental regulators. These proteins are known as wnt-2 (also known as irp), wnt-3 up to wnt-15. At least four members of this family are present in Drosophila; one of them, wingless (wg), is implicated in segmentation polarity.

All these proteins share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulfide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters.

Signal transduction by the Wnt family of ligands is mediated by the binding to the extracellular domain fz of Frizzled receptors. It can lead to either the activation of dishvelled proteins, inhibition of GSK-3 kinase, nuclear accumulation of β-catenin and activation of Wnt target genes or be coupled to the inositol signaling pathway and PKC activation, depending on the type of Frizzled receptor [5,6].

We selected a highly conserved region including three cysteines as a signature for this family of proteins.