Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues.
The frizzled (fz) locus of Drosophila encodes a protein (Fz) with a seven-transmembrane-domain profile characteristic of G-protein-coupled receptors. In Drosophila, genetic evidence suggests that Fz functions to transmit and transduce polarity signals in epidermal cells during hair and bristle development. We have isolated from a UMR 106 rat osteosarcoma cell library a cDNA (fz-1) encoding a predicted 641-residue protein (Fz-1) with 46% homology with Drosophila Fz. We also identified a second cDNA (fz-2) encoding a protein (Fz-2) of 570 amino acids that is 80% homologous with Fz-1, with divergence most evident in the extracellular domains. Southern blots of rat genomic DNA indicated that fz-1 and fz-2 represent distinct genes. Northern analysis revealed the presence of a single fz-1 mRNA (4.7 kilobases) and two fz-2 mRNAs (2.5 and 4.5 kilobases) in rat tissues. The fz-1 and fz-2 genes are widely expressed in rat tissues with the highest steady-state levels of mRNA in kidney, liver, heart, uterus, and ovary. fz-1 and -2 mRNA levels were greater in neonatal than in corresponding adult tissues. Treatment of UMR 106 cells with bone resorbing agents including parathyroid hormone, epidermal growth factor, and 1,25-dihydroxyvitamin D3 produced increases in fz-1 and -2 mRNA levels. We suggest that hormonal induction of Fz proteins in osteoblasts serves to promote intercellular signaling required for functional responses such as increased bone resorption. Fz-1 and Fz-2 may represent products of a gene family whose members serve as transducers or intercellular transmitters of signals required for normal morphogenesis and/or differentiated function in diverse tissues.
Chan
S D
SD
Endocrine Research Unit, Veterans Affairs Medical Center, San Francisco, California 94121.
Karpf
D B
DB
Fowlkes
M E
ME
Hooks
M
M
Bradley
M S
MS
Vuong
V
V
Bambino
T
T
Liu
M Y
MY
Arnaud
C D
CD
Strewler
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004330:Drosophila / Q000235:genetics*; D051157:Frizzled Receptors; D015723:Gene Library; D007668:Kidney / Q000502:physiology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D012516:Osteosarcoma; D011487:Protein Conformation; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D051157:Frizzled Receptors; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; C078603:Fzd1 protein, rat; C078604:Fzd2 protein, rat; D004247:DNA