Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila
Author(s) -
Louise Y Cheng,
Andrew P. Bailey,
Sally J. Leevers,
Timothy J. Ragan,
Paul C. Driscoll,
Alex P. Gould
Publication year - 2011
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2011.06.040
Subject(s) - biology , anaplastic lymphoma kinase , drosophila (subgenus) , lymphoma , cancer research , microbiology and biotechnology , genetics , medicine , immunology , gene , pleural effusion , malignant pleural effusion
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.
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