Figure 9.

PTTH and insulin signaling pathways in lepidopteran ecdysone secretion. PTTH: In both Bombyx and Manduca, PTTH has been shown to stimulate tyrosine kinase activity. We suggest that this leads to the phosphorylation of a postulated receptor substrate (modeled as Torso Receptor Substrate, TRS), capable of interacting with PLC (phospholipase C). PTTH is known to increase intracellular calcium, activate calcium-sensitive adenylyl cyclase (not shown), and to elevate cyclic AMP. TRS is postulated to recruit the adapter protein GRB2 and SOS, enhancing the activity of RAS and RAF, leading to known activation of MEK, ERK, and RSK. Cyclic AMP is also suggested to act via an effect on the MAPkinase pathway (dotted line). Insulin/Bombyxin: In both Bombyx and Manduca, insulin or bombyxin activate PI3K and Akt, which is presumed to increase the activity of TOR (target of rapamycin) through proteins not shown. TOR enhances translation by suppressing the translation inhibitor 4E-binding protein (4EBP), and activating p70 S6 kinase, which targets ribosomal protein S6. The primary difference seen between the prothoracic glands of Manduca and Bombyx is the ability of both insulin and PTTH to activate the insulin signaling pathway in Bombyx (PI3K, Akt, TOR, 4EBP) and by this pathway to stimulate ecdysone secretion (Gray curved arrow). By contrast, in Manduca, although PTTH stimulates the phosphorylation of 4EBP suggesting activation of PI3K (dotted line), the insulin signaling pathway is neither sufficient, nor required, for ecdysone synthesis. Instead, secretion is mediated by PTTH-stimulated activation of MAPkinases (Black curved arrow).