| Akt/PKB significantly regulates growth and metabolism in response to hormones and growth factors, including insulin. Genetic analysis in Drosophila has led to the identification of key components of the insulin signaling pathway. A genetic screen has implicated BiP, a major regulator of endoplasmic reticulum (ER) stress, as an interacting partner of Akt in Drosophila (Dakt1). Our results include a mechanism for the interaction between dBiP, the Drosophila homologue of BiP, and Dakt1. In particular, dBiP was found to contribute to the phosphorylation and hence activation of Dakt1. Further investigation of dBiP revealed that it is a major regulator of growth, and that it functions upstream of Dakt1 in growth control. A novel biological function for Dakt1 in the regulation of ER stress was also elucidated. In particular, Dakt1, in addition to dBiP, significantly repressed ER stress. Overall, our genetic data suggests a close mechanism between BiP and Akt in Drosophila. |
