HUMAN DISHEVELLED GENES CONSTITUTE A DHR-CONTAINING MULTIGENE FAMILY

Three human genes encoding proteins homologous to Drosophila Dishevell ed protein were cloned and characterized. Amino acid similarity betwee n the different Dishevelled proteins is concentrated in three highly c onserved regions. Two of these regions do not exhibit significant sequ ence similarity with other known proteins; the third is similar to the discs-large homology region, which was first found in a Drosophila Di scs-large tumor suppressor protein (also known as GLGF or PDZ domain). We produced antibodies against human Dishevelled-2 and demonstrated t hat it is a phosphoprotein and can be detected in all cell lines and h uman embryonic tissues examined. Indirect immunofluorescence indicates that it is found throughout the cytoplasm. Our results indicate that a human dishevelled genes constitute a multigene family and that Dishe velled proteins are highly conserved among metazoans. (C) 1997 Academi c Press.