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A Member of the Kekkon Protein Family Ryan Allis Sean Boyle
An Analysis of Kek1 Introduction Kek1 Kekkon Family A Member of the Kekkon Protein Family Ryan Allis Sean Boyle Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion
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Kek1 Characteristics Organism: Drosophila melanogaster
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
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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
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Transmembrane Images Introduction Kek1 Kekkon Family Kekkon Image
Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion
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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
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Kekkon Function Kek1 Kek2 & Kek6 kek1 Kek6
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
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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)
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Similar Genes In Mammalian Organisms
Introduction Kek1 LIGs have been identified in vertebrate genome (mice) AMIGO Alivin LRRs flanked by C-rich regions, a single Ig domain, and transmembrane region. Kekkon Family Kekkon Image Kekkon Background Kekkon Function Kek1 Research Global LIGs Conclusion
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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
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