Insulin receptor substrate family member IST-1 regulates the development of Caenorhabditis elegans age-1 and aap-1 mutants.

Insulin receptor substrate (IRS) is a class of adaptor proteins that mediate the activation of transmembrane tyrosine kinase receptors to downstream effectors. The IST-1 protein is the sole IRS present in Caenorhabditis elegans , which has been poorly studied in this animal model. Here, we show that ist-1 mutants develop normally but exhibit sterility, larval arrest and dauer phenotypes when combined with mutations in age-1 and aap-1 genes, which encode the catalytic and regulatory subunits of phosphatidylinositol 3-kinase (PI3K), respectively. In contrast, no major genetic interactions are observed with mutations in other genes of the worm insulin pathway, either upstream or downstream AGE-1 / AAP-1 . We conclude that IST-1 , the only IRS in C. elegans , functions as a positive regulator of PI3K in the canonical insulin pathway during development.