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Figure 2.2 A schematic illustration of downstream effectors of insulin/TOR in
Droso-
phila. Circulating Drosophila insulin-like peptides (DILPs) activate the insulin receptor
(InR) and promote cell growth through effectors (grey) that include PI3K/AKT which
affects the transcription factor FOXO. The TOR branch (green effectors) is activated
by intracellular amino acids imported through Slimfast, a membrane transporter. The
insulin pathway through AKT can also regulate TOR. Both pathways affect growth by
regulating common downstream effectors such as S6K, TIF-1A, and 4E-BP (orange).
suppressing Forkhead box Class O (FOXO) activity, a negative growth reg-
ulator, and also increases cellular energy levels through an upregulation of
glucose transporters in the cell membrane ( Junger et al., 2003; Kramer,
Davidge, Lockyer, & Staveley, 2003; Puig, Marr, Ruhf, & Tjian, 2003;
Puig & Tjian, 2005 ). Phosphorylation of FOXO by AKT results in the
translocation of FOXO from the nucleus to the cytosol which suppresses
its transcriptional activity. During nutritional deprivation, reduced insulin
signaling lowers PI3K/AKT activity, which promotes nuclear localization
of FOXO and suppresses cell growth.
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