A Large Family of Putative Transmembrane Receptors Homologous to the Product of the Drosophila Tissue Polarity Gene frizzled

doi:10.1074/jbc.271.8.4468

A Large Family of Putative Transmembrane Receptors Homologous to the Product of the Drosophila Tissue Polarity Gene frizzled(*)

From the (1)Departments of Molecular Biology and Genetics,
(2)Neuroscience,
(3)Neurology, and
(4)Ophthalmology,
(5)Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 and the
(6)Mammalian Genetics Laboratory, ABL Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702

Abstract

In Drosophila melanogaster, the frizzled gene plays an essential role in the development of tissue polarity as assessed by the orientation of cuticular structures. Through a combination of random cDNA sequencing, degenerate polymerase chain reaction amplification, and low stringency hybridization we have identified six novel frizzled homologues from mammals, at least 11 from zebrafish, several from chicken and sea urchin, and one from Caenorhabditis elegans. The complete deduced amino acid sequences of the mammalian and nematode homologues share with the Drosophila frizzled protein a conserved amino-terminal cysteine-rich domain and seven putative transmembrane segments. Each of the mammalian homologues is expressed in a distinctive set of tissues in the adult, and at least three are expressed during embryogenesis. As hypothesized for the Drosophila frizzled protein, the frizzled homologues are likely to act as transmembrane receptors for as yet unidentified ligands. These observations predict the existence of a family of signal transduction pathways that are homologous to the pathway that determines tissue polarity in Drosophila.

Footnotes

↵* This work was supported by the Howard Hughes Medical Institute, the Ruth and Milton Steinbach Fund, the Medical Scientist Training Program (to B. S. A.), and by the National Cancer Institute, DHHS, under contract with ABL. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(™)/EMBL Data Bank with accession number(s) U43205 and U43316-U43321.
↵¹ The abbreviations used are:

PCR

polymerase chain reaction

BLAST

basic local alignment search tool

RACE

rapid amplification of cDNA ends

RFLP

restriction fragment length polymorphism

IB

interspecific backcross

kb

kilobase pair(s).
↵²J. P. Macke, P. M. Smallwood, and J. Nathans, unpublished data.
↵³P. Bhanot, D. Andrew, Y. Wang, and J. Nathans, unpublished data.
↵⁴N. G. Copeland and N. A. Jenkins, unpublished results.
- Received November 1, 1995.