| Literature References | 1. WODARZ, A. AND NUSSE, R.
Mechanisms of Wnt signal transduction.
ANNU.REV.CELL DEV.BIOL. 14 59-88 (1998).
2. BEJSOVEC, A.
Signal transduction: Wnt signalling shows its versatility.
CURR.BIOL. 9 R684-R687 (1999).
3. DE FERRARI, G.V. AND INESTROSA, N.C.
Wnt signaling function in Alzheimer's disease.
BRAIN RES.BRAIN RES.REV. 33 1-12 (2000).
4. SEMENOV, M.V. AND SNYDER, M.
Human dishevelled genes constitute a DHR-containing multigene family.
GENOMICS 42 302-310 (1997).
5. PEIFER, M. AND POLAKIS, P.
Wnt signalling in oncogenesis and embryogenesis - a look outside the
nucleus.
SCIENCE 287 1606-1609 (2000).
6. MOON, R.T.
An introduction to non-canonical Wnt and Frizzled signaling.
SEMIN.CELL DEV.BIOL. 13 215 (2002).
7. GAVIN, B.J., MCMAHON, J.A. AND MCMAHON, A.P.
Expression of multiple novel Wnt-1/int-1-related genes during fetal and
adult mouse development.
GENES DEV. 4 2319-2332 (1990).
8. MCMAHON, J.A., MCMAHON, A.P. AND WEINBERG, R.A.
Essential function of Wnt-4 in mammary gland development downstream of
progesterone signaling.
GENES DEV. 14 650-654 (2000).
9. STARK, K., VAINIO, S., VASSILEVA, G. AND MCMAHON, A.P.
Epithelial transformation of metanephric mesenchyme in the developing
kidney regulated by Wnt-4.
NATURE 372 679-683 (1994).
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| Documentation | Wnt proteins constitute a large family of secreted molecules that are
involved in intercellular signalling during development. The name derives
from the first 2 members of the family to be discovered: int-1 (mouse) and
wingless (Drosophila) [1]. It is now recognised that Wnt signalling controls
many cell fate decisions in a variety of different organisms, including
mammals [2]. Wnt signalling has been implicated in tumorigenesis, early
mesodermal patterning of the embryo, morphogenesis of the brain and kidneys,
regulation of mammary gland proliferation and Alzheimer's disease [3,4].
Wnt-mediated signalling is believed to proceed initially through binding to
cell surface receptors of the frizzled family; the signal is subsequently
transduced through several cytoplasmic components to B-catenin, which enters
the nucleus and activates the transcription of several genes important in
development [5]. More recently, however, several non-canonical Wnt
signalling pathways have been elucidated that act independently of
B-catenin [6]. Members of the Wnt gene family are defined by their sequence
similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins
of ~350-400 residues in length, with orthologues identified in several,
mostly vertebrate, species. Very little is known about the structure of
Wnts as they are notoriously insoluble; in terms of primary structure, the
family is characterised by a signal sequence and an almost invariant pattern
of 23-24 conserved cysteines [1]. Fifteen major Wnt gene families have been
identified in vertebrates, with multiple subtypes within some classes.
Wnt-4 cDNA was isolated from mouse using a PCR-based strategy, where it was
found to be expressed in adult tissues, particularly in brain and lung [7].
Wnt-4 is believed to act downstream of progesterone signalling to play
an important role in mammary gland development [8]. Furthermore, mutations
in the Wnt-4 gene have been linked to kidney defects [9].
WNT4PROTEIN is a 4-element fingerprint that provides a signature for Wnt-4
proteins. The fingerprint was derived from an initial alignment of 7
sequences: the motifs were drawn from conserved regions spanning the N-
terminal half of the alignment, focusing on those sections that characterise
Wnt-4 proteins but distinguish them from related Wnt subtypes - motifs 1 and
2 lie between the putative signal peptide and the first conserved cysteine;
and motifs 3 and 4 reside in regions between other well-conserved N-terminal
cysteines. Two iterations on SPTR40_20f were required to reach convergence,
at which point a true set comprising 9 sequences was identified.
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