Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila

被引:174
作者
Cheng, Louise Y. [1 ]
Bailey, Andrew P. [1 ]
Leevers, Sally J. [3 ]
Ragan, Timothy J. [2 ]
Driscoll, Paul C. [2 ]
Gould, Alex P. [1 ]
机构
[1] Natl Inst Med Res, MRC, Div Dev Neurobiol, London NW7 1AA, England
[2] Natl Inst Med Res, MRC, Div Mol Struct, London NW7 1AA, England
[3] Canc Res UK London Res Inst, London WC2A 3PX, England
基金
英国医学研究理事会;
关键词
RECEPTOR TYROSINE KINASE; ASYMMETRIC CELL-DIVISION; INSULIN-LIKE PEPTIDES; PHOSPHOINOSITIDE; 3-KINASE; ACTIVATING MUTATIONS; SIGNALING PATHWAY; BRAIN-DEVELOPMENT; ALK KINASE; FAT-CELLS; LIFE-SPAN;
D O I
10.1016/j.cell.2011.06.040
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Developing animals survive periods of starvation by protecting the growth of critical organs at the expense of other tissues. Here, we use Drosophila to explore the as yet unknown mechanisms regulating this privileged tissue growth. As in mammals, we observe in Drosophila that the CNS is more highly spared than other tissues during nutrient restriction (NR). We demonstrate that anaplastic lymphoma kinase (Alk) efficiently protects neural progenitor (neuroblast) growth against reductions in amino acids and insulin-like peptides during NR via two mechanisms. First, Alk suppresses the growth requirement for amino acid sensing via Slimfast/Rheb/TOR complex 1. And second, Alk, rather than insulin-like receptor, primarily activates PI3-kinase. Alk maintains PI3-kinase signaling during NR as its ligand, Jelly belly (Jeb), is constitutively expressed from a glial cell niche surrounding neuroblasts. Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors.
引用
收藏
页码:435 / 447
页数:13
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