CAENORHABDITIS-ELEGANS AKT PKB TRANSDUCES INSULIN RECEPTOR-LIKE SIGNALS FROM AGE-1 PI3 KINASE TO THE DAF-16 TRANSCRIPTION FACTOR/

A neurosecretory pathway regulates a reversible developmental arrest a nd metabolic shift at the Caenorhabditis elegans dauer larval stage, D efects in an insulin-like signaling pathway cause arrest at the dauer stage. We show here that two C. elegans Akt/PKB homologs, akr-l and ak t-2, transduce insulin receptor-like signals that inhibit dauer arrest and that AKT-1 and AKT-2 signaling are indispensable for insulin rece ptor-like signaling in C. elegans, A loss-of-function mutation in the Pork head transcription factor DAF-16 relieves the requirement far Akt /PKB signaling, which indicates that AKT-1 and AKT-2 function primaril y to antagonize DAF-16. This is the first evidence that the major targ et of Akt/PKB signaling is a transcription factor. An activating mutat ion in akt-1, revealed by a genetic screen, as well as increased dosag e of wild-type akt-1 relieves the requirement for signaling from AGE-1 PI3K, which acts downstream of the DAF-2 insulin/IGF-1 receptor homol og. This demonstrates that Akt/PKB activity is not necessarily depende nt on AGE-1 PI3K activity. akt-1 and akt-2 are expressed in overlappin g patterns In the nervous system and in tissues that are remodeled dur ing dauer formation.