Reference Report

Reference
Citation	Gouzi, J.Y., Moressis, A., Walker, J.A., Apostolopoulou, A.A., Palmer, R.H., Bernards, A., Skoulakis, E.M. (2011). The receptor tyrosine kinase alk controls neurofibromin functions in Drosophila growth and learning. PLoS Genet. 7(9): e1002281. (Export to RIS)
FlyBase ID	FBrf0216258
Publication Type	Research paper
PubMed ID	21949657
PubMed 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.
DOI	10.1371/journal.pgen.1002281
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Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS Genet.
Title	PLoS Genetics
Publication Year	2005-
ISBN/ISSN	1553-7404 1553-7390
Data from Reference
Alleles (24)
	Alk¹ Alk⁹ Alk^{act.Scer\UAS.T:Ivir\HA1} Alk^{EC.Scer\UAS.T:Hsap\MYC} Alk^GD42 Alk^KK102942 Alk^Scer\UAS.cLa jeb^Scer\UAS.cVa Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} Nf1^E1 Nf1^E2 Nf1^Scer\UAS.cWa rl^Sem.Scer\UAS Scer\GAL4^386Y Scer\GAL4^Alk.38 Scer\GAL4^c747 Scer\GAL4^Ccap.PP Scer\GAL4^elav-C155 Scer\GAL4^ey-OK107 Scer\GAL4^Ilp2.PR Scer\GAL4^Mef2.247 Scer\GAL4^Ras64B.PW Scer\GAL80^Mef2.PT Scer\GAL80^ts.αTub84B
Constructs (16)
	P{Alk-GAL4.38} P{Ccap-GAL4.P} P{GD42} P{Ilp2-GAL4.R} P{KK102942} P{Mef2-GAL4.247} P{Mef2-GAL80.T} P{Ras64B-GAL4.W} P{tubP-GAL80^ts} P{UAS-Alk.act.HA} P{UAS-Alk.EC.MYC} P{UAS-Alk.L} P{UAS-jeb.V} P{UAS-mCD8::GFP.L} P{UAS-Nf1.W} P{UAS-Sem}
Genes (8)
	Alk jeb Mmus\Cd8a Nf1 Ras64B rl Scer\GAL4 Scer\GAL80
Insertions (4)
	P{GawB}386Y P{GawB}c747 P{GawB}elav^C155 P{GawB}ey^OK107
Natural transposons (1)
	P-element
Transcripts (2)
	Scer\GAL4^Alk.38RA Scer\GAL4^Ras64B.PWRA