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Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo
Author(s) -
Lorén Christina E.,
Scully Audra,
Grabbe Caroline,
Edeen Philip T.,
Thomas John,
McKeown Michael,
Hunter Tony,
Palmer Ruth H.
Publication year - 2001
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.2001.00440.x
Subject(s) - biology , drosophila melanogaster , receptor tyrosine kinase , mapk/erk pathway , receptor protein tyrosine kinases , mesoderm , genetics , microbiology and biotechnology , signal transduction , embryonic stem cell , gene
BackgroundThe 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 .ResultsWe 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 .ConclusionIn 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 .