title: The ligand Jelly Belly (Jeb) activates the Drosophila Alk RTK to drive PC12 cell differentiation, but is unable to activate the mouse ALK RTK.
abstract: The Drosophila Alk receptor tyrosine kinase (RTK) drives founder cell specification in the developing visceral mesoderm and is crucial for the formation of the fly gut. Activation of Alk occurs in response to the secreted ligand Jelly Belly. No homologues of Jelly Belly are described in vertebrates, therefore we have approached the question of the evolutionary conservation of the Jeb-Alk interaction by asking whether vertebrate ALK is able to function in Drosophila. Here we show that the mouse ALK RTK is unable to rescue a Drosophila Alk mutant, indicating that mouse ALK is unable to recognise and respond to the Drosophila Jeb molecule. Furthermore, the overexpression of a dominant-negative Drosophila Alk transgene is able to block the visceral muscle fusion event, which an identically designed dominant-negative construct for the mouse ALK is not. Using PC12 cells as a model for neurite outgrowth, we show here for the first time that activation of dAlk by Jeb results in neurite extension. However, the mouse Alk receptor is unable to respond in any way to the Drosophila Jeb protein in the PC12 system. In conclusion, we find that the mammalian ALK receptor is unable to respond to the Jeb ligand in vivo or in vitro. These results suggest that either (i) mouse ALK and "mouse Jeb" have co-evolved to the extent that mALK can no longer recognise the Drosophila Jeb ligand or (ii) that the mALK RTK has evolved such that it is no longer activated by a Jeb-like molecule in vertebrates.
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå S-901 87, Sweden.
authors.forename: Hai-Ling
authors.initials: HL
authors.lastname: Yang
authors.forename: Therese
authors.initials: T
authors.lastname: Eriksson
authors.forename: Emma
authors.initials: E
authors.lastname: Vernersson
authors.forename: Marc
authors.initials: M
authors.lastname: Vigny
authors.forename: Bengt
authors.initials: B
authors.lastname: Hallberg
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Palmer
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D003433:Crosses, Genetic; D017931:DNA Primers; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D019143:Evolution, Molecular; D047468:Immunoprecipitation; D007814:Larva / Q000033:anatomy & histology; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology; D016716:PC12 Cells; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D019076:Transgenes / Q000235:genetics
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; C440828:jeb protein, Drosophila; C000626174:Alk protein, mouse; C000626175:Alk protein, rat; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases