Transcript An Analysis of Kek1 - Indiana University

Introduction
Kek1
An Analysis of Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
A Member of the Kekkon
Protein Family
Kek1 Research
Global LIGs
Conclusion
Ryan Allis
Sean Boyle
Kek1 Characteristics
Introduction
Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
Kek1 Research
Global LIGs
Conclusion
• Organism: Drosophila melanogaster
• Epidermal Growth Factor Receptor
(EGFR) Signaling
• Neuronal pathfinding
• Transmembrane protein
• Founding member of kekkon family
Kekkon Family Components
Introduction
Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
Kek1 Research
Global LIGs
Conclusion
• 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
Transmembrane Images
Introduction
Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
Kek1 Research
Global LIGs
Conclusion
Kekkon Family Background
Introduction
Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
Kek1 Research
Global LIGs
Conclusion
• 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
Kekkon Function
Introduction
Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
Kek1 Research
Global LIGs
Conclusion
• 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
Introduction
Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
Kek1 Research
Global LIGs
Conclusion
Kek1 Mutation Research
(Drosophila)
• 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
Magnified
image crosssection of
follicle cells
(wt, class1,
class2)
Similar Genes In Mammalian
Organisms
Introduction
Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
Kek1 Research
Global LIGs
Conclusion
• LIGs have been identified in
vertebrate genome (mice)
• AMIGO
• Alivin
• LRRs flanked by C-rich regions, a
single Ig domain, and transmembrane
region.
Conclusions
Introduction
Kek1
Kekkon Family
Kekkon Image
Kekkon Background
Kekkon Function
Kek1 Research
Global LIGs
Conclusion
• 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