Abstract: H. Bahar ŞAHIN

Insulin Pathway Related Salt Inducible Kinases in Fruit Fly Retina Development

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H. Bahar ?ahin (1), Sercan Sayin (2), Arzu Celik (3)

(1) Kadir Has University, Department of Bioinformatics and Genetics, Fatih, Istanbul,Turkey
(2) Max Planck Institute of Neurobiology, Munich, Germany
(3) Bogazici University, Department of Molecular Biology and Genetics, Bebek, Istanbul, Turkey

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Salt inducible kinases (SIKs) are Ser/Thr kinases members of AMPK-RK family. Upon regulation by glucagon induced PKA signal, SIKs regulate IRS-1, CRTC activity, and in turn CREB. Via the Insulin induced Akt, SIKs are known to inhibit CREB and CRTC. Besides the long known role in insulin pathway, SIKs are target of a master tumor suppressor kinase Lkb-1; which is supported by many instances showing SIKs involvement in cancer progression. In this study, we model the highly conserved SIK2 and SIK3 homologs in the fruit fly, Drosophila melanogaster. Like the mammalian ortholog, Drosophila SIK2 interacts with the FGF pathway in the course of insulin metabolism; while SIK3 was shown to affect glucose/lipid homeostasis, skeletal and adipocyte development. Yet the molecular interactions SIKs goes through remain largely unknown. We started to characterize the tumorigenic role of SIK2 and SIK3 in nervous system development using the Drosophila compound eyes as a model. We have seen that, SIKs can induce tumorigenesis in a suitable niche. In order to study the SIK role further, we have generated the controllable expression of SIK3, SIK3 null mutants, and the fluorescent-tagged proteins of SIK2 and SIK3 to elucidate expression patterns. We have also shown that both SIK2 and SIK3 are involved in eye development, regulating eye size and cell specification events. Using scanning electron microscopy, we have seen that bristles and lenses are disrupted in mutants. To understand the defect in more detail, we analyzed late larval and early pupal expression of SIK2 and SIK3, using the fluorescent-tagged constructs, since no antibody is available for fly homolog of SIK2. We have seen that both genes have neural expression, although pattern is different. Thus, in this project, our aim is to attribute a defined role in neural development and cell specification to Drosophila SIK genes.