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. 2003 Dec;23(24):9117–9126. doi: 10.1128/MCB.23.24.9117-9126.2003

FIG. 6.

FIG. 6.

Models of the insulin-signaling pathway in Drosophila and regulation of d4E-BP by phosphorylation. (A) A common pathway regulates 4E-BP and S6K. The regulation of 4E-BP is dependent on signaling from Inr-PI3K-Akt-TSC and TOR. The regulation of S6K is also effected by PDK1 and the same upstream elements. The different size of the Akt typeface is to illustrate that the intensity of signaling toward TSC affects 4E-BP and S6K differentially. (B) The pattern of phosphorylation of d4E-BP as observed by IEF-SDS-PAGE may result from one of three possible models. (i) In the primed model, d4E-BP is already phosphorylated at Thr37 and is subsequently phosphorylated on one additional site, Thr46, after insulin stimulation. (ii) In the sequential model, d4E-BP is phosphorylated on Thr37 and then Thr46 (or vice versa). (iii) In the coordinated model, d4E-BP is phosphorylated coordinately on Thr37 and Thr46.