canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila.

Miyamoto, Hiroshi; Nihonmatsu, Itsuko; Kondo, Shunzo; Ueda, Ryo; Togashi, Shin; Hirata, Kazuo; Ikegami, Yuko; Yamamoto, Daisuke

doi:10.1101/gad.9.5.612

Cited by 114 publications

(110 citation statements)

References 74 publications

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“…These functions of Ras1 are likely to be mediated by one of the Ras eectors, D-raf/Raf. Two Drosophila genes coding for possible Ras eectors Canoe/AF6 (Miyamoto et al, 1995;Matsuo et al, 1997) and phosphoinositide 3-kinase (Leevers et al, 1996) have also been identi®ed, but their roles in the Ras pathway have not yet been determined. In the present work, the novel phenotype caused by another downstream-signaling molecule, Ral, indicates that Ral has a function distinct from that of the Raf/ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development

et al. 1999

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The small GTP-binding protein Ral is activated by RalGDS, one of the eector molecules for Ras. Active Ral binds to a GTPase activating protein for CDC42 and Rac. Although previous studies suggest a role for Ral in the regulation of CDC42 and Rac, which are involved in arranging the cytoskeleton, its in vivo function is largely unknown. To examine the eect of overexpressing Ral on development, transgenic Drosophila were generated that overexpress wild-type or mutated Ral during eye development. While wild-type Ral caused no developmental defects, expression of a constitutively activated protein resulted in a rough eye phenotype. Activated Ral did not aect cell fate determination in the larval eye discs but caused severe disruption of the ommatidial organization later in pupal development. Phalloidin staining showed that activated Ral perturbed the cytoskeletal structure and cell shape changes during pupal development. This phenotype is similar to that caused by RhoA overexpression. In addition, the phenotype was synergistically enhanced by the coexpression of RhoA. These results suggest that Ral functions to control the cytoskeletal structure required for cell shape changes during Drosophila development.

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Section: Discussionmentioning

confidence: 99%

Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development

et al. 1999

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“…Further genetic and biochemical evidence indicates that Cno interacts with Drosophila ZO-1, whose mammalian homolog is a known component of cellular junctions and member of the MAGUK family of proteins containing protein-binding PDZ and guanylate kinase domains (Itoh et al, 1993;Stevenson et al, 1986). Interestingly, cno encodes a protein that also contains a PDZ domain and, in addition, contains motifs that resemble kinesin, myosin V, and Ras binding domains (Miyamoto et al, 1995;Ponting, 1995). Examination of Cno protein distribution in¯y embryos reveals broad tissue distribution but restricted subcellular localization to the adherens junctions of epithelial cells (Takahashi et al, 1998).…”

Section: Cell Junction Proteinsmentioning

confidence: 99%

Stress signaling in Drosophila

1999

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“…The PDZ-domain protein AF6 was previously reported to interact with the amino acids RMEYIV at the C terminus of Jagged1 in a directed yeast two-hybrid analysis (13). Moreover, AF6 is the mammalian homolog of Drosophila canoe, which has been genetically linked to the Notch pathway (46). Therefore, we tested the ability of the GST-JAGGED1 fusion proteins to bind AF6.…”

Section: Deletion Of Either the Extracellular Or Intracellular Domainmentioning

confidence: 99%

“…More specifically, we assessed if the PDZ-domain protein AF6 could bind the intracellular domain of JAGGED1, since AF6 was previously reported to interact with six residues (RMEYIV) found at the C terminus of Jagged1 using a directed yeast two-hybrid analysis (13). Furthermore, AF6 is the mammalian homolog of Drosophila canoe which has been genetically linked to the Notch pathway (46). Our data demonstrates that the interaction between JAGGED1 and AF6 occurs in a PDZ-dependent manner, since deletion of the PDZ-ligand of JAGGED1 or of the PDZ-domain of AF6 abolished this interaction (Fig.…”

Section: Fig 5 An Intact Pdz-ligand Is Required For Activation Of Thementioning

confidence: 99%

The C-terminal PDZ-Ligand of JAGGED1 Is Essential for Cellular Transformation

Ascano

Beverly

Capobianco

2003

Journal of Biological Chemistry

111

113

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JAGGED1 is a member of the Delta/Serrate/Lag-2 (DSL) family of proteins that are cell-bound ligands for Notch receptors. Initiation of Notch signaling occurs through a series of proteolytic events upon the binding of Notch to a DSL protein presented on neighboring cells. Whether DSL proteins themselves are capable of initiating an intrinsic signaling mechanism within the cell they are expressed is not known. Aberrant misexpression of JAGGED1 and DELTA1 has been documented in several human tumors; however, the mechanism by which misexpression of JAGGED1 contributes to oncogenesis has not been elucidated. We report that expression of human JAGGED1 transforms RKE cells in culture, therefore providing a model system to elucidate the function of DSL proteins. JAGGED1-mediated transformation occurs in a dose-dependent manner and requires a PDZ-ligand at the C terminus. Mutation of the PDZ-ligand did not affect the ability of JAGGED1 to initiate Notch signaling in neighboring cells. However, the PDZ-ligand is required for changes in the expression of JAGGED1 target genes and transcriptional activation of luciferase reporter constructs. Our data indicate the existence of a novel PDZ-dependent signaling pathway intrinsic to JAGGED1. We propose a bi-directional signaling model such that DSL proteins may have two distinct functions: to initiate Notch signaling in a neighboring cell and to initiate a PDZ-dependent signaling mechanism in the DSL-expressing cell. Moreover, we conclude that this intrinsic signaling mechanism of JAGGED1 may partly provide a link between aberrant misexpression of JAGGED1 and tumorigenesis.

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canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila.

Cited by 114 publications

References 74 publications

Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development

Ectopic expression of constitutively activated Ral GTPase inhibits cell shape changes during Drosophila eye development

Stress signaling in Drosophila

The C-terminal PDZ-Ligand of JAGGED1 Is Essential for Cellular Transformation

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