Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo.
BACKGROUND
The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the product of the t(2;5) chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism 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 described.


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-length 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 both mammalian and Drosophila ALK reveals that the ALK family of RTKs contains a newly identified MAM domain within their extracellular domains. Like its mammalian counterpart, DAlk appears to be expressed in the developing CNS by in situ analysis. However, in addition to expression of DAlk in the Drosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident with activated ERK.


CONCLUSIONS
In this paper we describe a Drosophila melanogaster Alk RTK which is expressed in the developing embryonic mesoderm and CNS. Our data provide 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 that DAlk fulfils the criteria of the missing RTK pathway, leading to ERK activation in the developing visceral mesoderm.
Lorén
C E
CE
Umeå Center for Molecular Pathogenesis, Building 6L, Umeå University, S-901 87, Sweden.
Scully
A
A
Grabbe
C
C
Edeen
P T
PT
Thomas
J
J
McKeown
M
M
Hunter
T
T
Palmer
R H
RH
D000595:Amino Acid Sequence; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D017344:Genes, Insect; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D016415:Sequence Alignment; D015398:Signal Transduction
D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases