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PLoS Genet. 2011 Sep;7(9):e1002281. doi: 10.1371/journal.pgen.1002281. Epub 2011 Sep 15.

The receptor tyrosine kinase Alk controls neurofibromin functions in Drosophila growth and learning.

Author information

1
Institute of Cellular and Developmental Biology, Biomedical Sciences Research Centre "Alexander Fleming," Vari, Greece.

Abstract

Anaplastic Lymphoma Kinase (Alk) is a Receptor Tyrosine Kinase (RTK) activated in several cancers, but with largely unknown physiological functions. We report two unexpected roles for the Drosophila ortholog dAlk, in body size determination and associative learning. Remarkably, reducing neuronal dAlk activity increased body size and enhanced associative learning, suggesting that its activation is inhibitory in both processes. Consistently, dAlk activation reduced body size and caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and interact functionally in the nervous system. Importantly, genetic or pharmacological inhibition of dAlk rescued the reduced body size, adult learning deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mutant phenotypes. These results identify dAlk as an upstream activator of dNf1-regulated Ras signaling responsible for several dNf1 defects, and they implicate human Alk as a potential therapeutic target in NF1.

PMID:
21949657
PMCID:
PMC3174217
DOI:
10.1371/journal.pgen.1002281
[Indexed for MEDLINE]
Free PMC Article
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