Biochemical characterization of the Drosophila insulin receptor kinase and longevity-associated mutants.

ABSTRACT: Drosophila melanogaster (fruit fly) insulin receptor (D-IR) is highly homologous to the human counterpart. Like the human pathway, D-IR responds to numerous insulin-like peptides to activate cellular signals that regulate growth, development, and lipid metabolism in fruit flies. Allelic mutations in the D-IR kinase domain elevate life expectancy in fruit flies. We developed a robust heterologous expression system to express and purify wild-type and longevity-associated mutant D-IR kinase domains to investigate enzyme kinetics and substrate specificities. D-IR exhibits remarkable similarities to the human insulin receptor kinase domain but diverges in substrate preferences. We show that longevity-associated mutations reduce D-IR catalytic activity. Deletion of the unique kinase insert domai

SUBMITTER: Krishnan H 

PROVIDER: S-EPMC11284340 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature