An Analysis of Kek1

1. An Analysis of Kek1 Introduction Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research A Member of the Kekkon Protein Family Ryan Allis Sean Boyle Global LIGs Conclusion

2. Kek1 Characteristics Introduction • Organism: Drosophila melanogaster • Epidermal Growth Factor Receptor (EGFR) Signaling • Neuronal pathfinding • Transmembrane protein • Founding member of kekkon family Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion

3. Kekkon Family Components Introduction • 7 Leucine Rich Regions (LRR) • 1 Immunoglobulin (Ig) • N Glycosylation • C & N Caps • Highly divergent cytoplasmic tails • Regions outside LRR consensus • Share identity • Possible specific protein interactions Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion

4. Transmembrane Images Introduction Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion

5. Kekkon Family Background Introduction • Kekkon family proposed to have expanded from single ancestral gene • Orthologues known in arthropods, but few known in vertebrates • Honey Bee (Apis mellifera) • Mosquito (Anopheles gambiae) • ~300 million years • Ig & LRR are 2nd most prevalent in Metazoans • Very rarely together • 9 in Drosophila • 6 in Kekkon Family Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion

6. Kekkon Function Introduction • Kek1 • LRR2 and transmembrane region required for EGFR inhibition • knockouts exhibit increased spacing between dorsal appendages • Kek2 & Kek6 • thought to form complex - CAM (Cell Adhesion Molecules) • kek1  Kek6 • Possible overlap of Kek function () • Kek1, Kek2, & Kek3 LRR3 share motif “L*VE*DLS” • Possible common binding partner Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion

7. Kek1 Mutation Research (Drosophila) Introduction • 10 Suppressors range from partial to complete LOF • Class I Alleles • Class II Alleles • All are single residue mutations that disrupt the ability to inhibit EGFR • All located in extracellular domain Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion Magnified image cross-section of follicle cells (wt, class1, class2)

8. Similar Genes In Mammalian Organisms Introduction • LIGs have been identified in vertebrate genome (mice) • AMIGO • Alivin • LRRs flanked by C-rich regions, a single Ig domain, and transmembrane region. Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion

9. Conclusions Introduction • Kekkon family involved in important health related functions • Development • EGFR • Neuronal Pathfinding • Kekkon family protein structure found in mammalian organisms. • Have yet to be identified in Homo sapiens • Discovery could lead to much greater understanding of human growth factor and neuron development Kek1 Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion