Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo

Background: The mammalian receptor protein tyrosine kinase (RTK), Anaplasti c Lymphoma Kinase (ALK), was first described as the product of the t(2;5) c hromosomal translocation found in non-Hodgkin's lymphoma. While the mechani sm of ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been descri bed. Results: We describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to band 53 on the right arm of the second chromosome. Full-l ength DALk cDNA encodes a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK but also with the orphan RTK LTK. Analysis of b oth mammalian and Drosophila ALK reveals that the ALK family of RTKs contai ns a newly identified IMAM domain within their extracellular domains. Like its mammalian counterpart, DALk appears to be expressed in the developing C NS by in situ analysis. However, in addition to expression of DAlk in the D rosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident wit h activated ERK. Conclusion: In this paper we describe a Drosophila melanogaster Alk RTK whi ch is expressed in the developing embryonic mesoderm and CNS. Our data prov ide evidence for the existence of a DAlk RTK pathway in Drosophila. We show that ERK participates in this pathway, and that it is activated by DAlk in vivo. Expression patterns of dALK, together with activated ERK, suggest th at DAlk fulfils the criteria of the missing RTK pathway, leading to ERK act ivation in the developing visceral mesoderm.