Department of Life Science and Institute of Molecular Biology, National Chung-Cheng University, Chia-Yi 621, Taiwan.
Mech Dev. 2009 Oct;126(10):781-90. doi: 10.1016/j.mod.2009.08.005. Epub 2009 Sep 4.
The TOR and Jak/STAT signal pathways are highly conserved from Drosophila to mammals, but it is unclear whether they interact during development. The proline-rich Akt substrate of 40 kDa (PRAS40) mediates the TOR signal pathway through regulation of TORC1 activity, but its functions in TORC1 proved in cultured cells are controversial. The Drosophila gene Lobe (L) encodes the PRAS40 ortholog required for eye cell survival. L mutants exhibit apoptosis and eye-reduction phenotypes. It is unknown whether L regulates eye development via regulation of TORC1 activity. We found that reducing the L level, by hypomorphic L mutation or heterozygosity of the null L mutation, resulted in ectopic expression of unpaired (upd), which is known to act through the Jak/STAT signal pathway to promote proliferation during eye development. Unexpectedly, when L was reduced, decreasing Jak/STAT restored the eye size, whereas increasing Jak/STAT prevented eye formation. We found that ectopic Jak/STAT signaling and apoptosis are mutually dependent in L mutants, indicating that L reduction makes Jak/STAT signaling harmful to eye development. In addition, our genetic data suggest that TORC1 signaling is downregulated upon L reduction, supporting the idea that L regulates eye development through regulation of TORC1 activity. Similar to L reduction, decreasing TORC1 signaling by dTOR overexpression results in ectopic upd expression and apoptosis. A novel finding from our data is that dysregulated TORC1 signaling regulates the expression of upd and the function of the Jak/STAT signal pathway in Drosophila eye development.
TOR 和 Jak/STAT 信号通路在从果蝇到哺乳动物的过程中高度保守，但它们在发育过程中是否相互作用尚不清楚。富含脯氨酸的 Akt 底物 40 kDa（PRAS40）通过调节 TORC1 活性来介导 TOR 信号通路，但它在培养细胞中被证明具有 TORC1 功能的作用存在争议。果蝇基因 Lobe（L）编码眼细胞存活所必需的 PRAS40 同源物。L 突变体表现出细胞凋亡和眼睛缩小表型。尚不清楚 L 是否通过调节 TORC1 活性来调节眼睛发育。我们发现，通过减弱 L 的水平，即通过 L 突变的弱等位基因或 L 缺失突变的杂合性，导致未配对（upd）的异位表达，已知 upd 通过 Jak/STAT 信号通路发挥作用，以促进眼睛发育过程中的增殖。出乎意料的是，当 L 减少时，降低 Jak/STAT 恢复了眼睛大小，而增加 Jak/STAT 则阻止了眼睛的形成。我们发现，在 L 突变体中，异位 Jak/STAT 信号和细胞凋亡是相互依赖的，表明 L 减少使 Jak/STAT 信号对眼睛发育有害。此外，我们的遗传数据表明，L 减少后 TORC1 信号被下调，支持了 L 通过调节 TORC1 活性来调节眼睛发育的观点。类似于 L 减少，通过 dTOR 过表达降低 TORC1 信号会导致 upd 的异位表达和细胞凋亡。我们的数据中的一个新发现是，失调的 TORC1 信号调节 upd 的表达和 Jak/STAT 信号通路在果蝇眼睛发育中的功能。
