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Akap200 suppresses the effects of Dv-cbl expression in the Drosophila eye

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Abstract

The Drosophila melanogaster orthologue of the c-Cbl proto-oncogene acts to downregulate signalling from receptor tyrosine kinases by enhancing endocytosis of activated receptors. Expression of an analogue of the C-terminally truncated v-Cbl oncogene, Dv-cbl, in the developing Drosophila eye conversely leads to excess signalling and disruption to the well-ordered adult compound eye. Co-expression of activated Ras with Dv-cbl leads to a severe disruption of eye development. We have used a transposon-based inducible expression system to screen for molecules that can suppress the Dv-cbl phenotype and have identified an allele that upregulates the A-kinase anchoring protein, Akap200. Overexpression of Akap200 not only suppresses the phenotype caused by Dv-cbl expression, but also the severe disruption to eye development caused by the combined expression of Dv-cbl and activated Ras. Akap200 is also endogenously expressed in the developing Drosophila eye at a level that modulates the effects of excessive signalling caused by expression of Dv-cbl.

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Acknowledgments

The authors would like to thank the Bloomington Stock Center, Kyoto Drosophila Genetic Resource Center, Vienna Drosophila RNAi Center and the Australian Drosophila Biomedical Research Support Facility for providing Drosophila strains and the Developmental Studies Hybridoma Bank for providing antibodies. We would like to thank Franca Casagranda for assistance with qRT-PCR and Robb de Iongh for assistance with in situ hybridisation. This work was sponsored by the National Health and Medical Research Council Project Grant 350316 to GH and HR.

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Authors and Affiliations

  1. Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, 3010, Australia

    Rowena T. Sannang, Hannah Robertson, Nicole A. Siddall & Gary R. Hime

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  1. Rowena T. Sannang
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  2. Hannah Robertson
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  3. Nicole A. Siddall
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  4. Gary R. Hime
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Correspondence to Gary R. Hime.

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Sannang, R.T., Robertson, H., Siddall, N.A. et al. Akap200 suppresses the effects of Dv-cbl expression in the Drosophila eye. Mol Cell Biochem 369, 135–145 (2012). https://doi.org/10.1007/s11010-012-1376-x

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  • DOI: https://doi.org/10.1007/s11010-012-1376-x

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