A new member of the frizzled family from Drosophila functions as a Wingless receptor

Bhanot, Purnima; Brink, Marcel R.M. van den; Samos, Cindy Harryman; Hsieh, Jen Chih; Wang, Yanshu; Macke, Jennifer P.; Andrew, Deborah J.; Nathans, Jeremy; Nusse, Roel

doi:10.1038/382225a0

Cited by 1,356 publications

(986 citation statements)

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“…Genetic and biochemical data have led to the consensus view that the Frizzled (Fz) molecules are primary receptors for Wnts [2]. Frizzled receptors are 7 transmembrane molecules with a long amino-terminal extension called CRD (cysteine-rich domain).…”

Section: Wnt Receptorsmentioning

confidence: 99%

“…Frizzled receptors are 7 transmembrane molecules with a long amino-terminal extension called CRD (cysteine-rich domain). Wnt proteins bind directly to the CRD of Fz [2][3][4]. Wnt signaling requires not only a functional Fz, but also the presence of a long single pass transmembrane molecule of the LRP (LDL receptor related protein) class, identified as the gene arrow in Drosophila [5] and as LRP5 or 6 in vertebrates.…”

Section: Wnt Receptorsmentioning

confidence: 99%

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Wnt signaling in disease and in development

2005

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ABSCTACTThe highly conserved Wnt secreted proteins are critical mediators of cell-to-cell signaling during development of animals. Recent biochemical and genetic analyses have led to significant insight into understanding how Wnt signals work. The catalogue of Wnt signaling components has exploded. We now realize that multiple extracellular, cytoplasmic, and nuclear components modulate Wnt signaling. Moreover, receptor-ligand specificity and multiple feedback loops determine Wnt signaling outputs. It is also clear that Wnt signals are required for adult tissue maintenance. Perturbations in Wnt signaling cause human degenerative diseases as well as cancer.

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Section: Wnt Receptorsmentioning

confidence: 99%

Section: Wnt Receptorsmentioning

confidence: 99%

Wnt signaling in disease and in development

2005

Self Cite

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“…The receptors for Wnts have been identi®ed as a class of seven transmembrane proteins known as Frizzled (Fz) (Bhanot et al, 1996). The ligandreceptor interaction is facilitated by extracellular proteoglycans and inhibited by Fz-related proteins, dickkopf, and cerberus.…”

Section: A Brief Overview Of the Wnt Signaling Pathwaymentioning

confidence: 99%

Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer

2000

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Wnt-1 was ®rst identi®ed as a protooncogene activated by viral insertion in mouse mammary tumors. Transgenic expression of this gene using a mouse mammary tumor virus LTR enhancer causes extensive ductal hyperplasia early in life and mammary adenocarcinomas in approximately 50% of the female transgenic (TG) mice by 6 months of age. Metastasis to the lung and proximal lymph nodes is rare at the time tumors are detected but frequent after the removal of the primary neoplasm. The potent mitogenic e ect mediated by Wnt-1 expression does not require estrogen stimulation; tumors form after an increased latency in estrogen receptor a-null mice. Several genetic lesions, including inactivation of p53 and over-expression of Fgf-3, collaborate with Wnt-1 in leading to mammary tumors, but loss of Sky and inactivation of one allele of Rb do not a ect the rate of tumor formation in Wnt-1 TG mice.

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“…The developmental Northern blot was kindly provided by R Nusse and is referenced in Bhanot et al (1996).…”

Section: Northern Analysismentioning

confidence: 99%

D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding sites

Hime

Dhungat

et al. 1997

Oncogene

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The c-Cbl proto-oncogene encodes a multidomain phosphoprotein that has been demonstrated to interact with a wide range of signalling proteins. The biochemical function of c-Cbl in these complexes is, however, unclear. Recent studies with the C. elegans Cbl homologue, sli-1, have suggested that Cbl proteins may act as negative regulators of EGF receptor (EGFR) signalling. As the EGFR and other protein tyrosine kinase receptor signalling pathways are highly conserved between insects and vertebrates, we sought a Drosophila homologue of cCbl for a detailed genetic analysis. We report here that Drosophila melanogaster has a single gene, D-cbl, that is homologous to c-cbl. We ®nd that D-cbl encodes a 52 kDa protein that has a high degree of similarity to cCbl and SLI-1 across novel phosphotyrosine-binding (PTB) and RING ®nger domains. Surprisingly, however, D-Cbl is C-terminally truncated relative to c-Cbl and SLI-1 and consequently is unable to bind SH3-domain containing adaptor proteins, including the Drosophila Grb2 homologue, Drk. Although the D-Cbl protein lacks Drk binding sites it can nevertheless associate with a tyrosine phosphorylated protein, or is itself tyrosine phosphorylated in an DER dependent manner and associates with activated Drosophila EGF receptors (DER) in vivo. Consistent with a role for D-Cbl in DER dependent patterning in the embryo and adult, DCbl is expressed at a high level in early embryos and throughout the imaginal discs in third instar larvae. This study forms the basis for future genetic analysis of DCbl, aimed at gaining insights into the role of Cbl proteins in signal transduction.

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A new member of the frizzled family from Drosophila functions as a Wingless receptor

Cited by 1,356 publications

References 46 publications

Wnt signaling in disease and in development

Wnt signaling in disease and in development

Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer

D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding sites

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