title: Jelly belly protein activates the receptor tyrosine kinase Alk to specify visceral muscle pioneers.
abstract: The secreted protein Jelly belly (Jeb) is required for an essential signalling event in Drosophila muscle development. In the absence of functional Jeb, visceral muscle precursors are normally specified but fail to migrate and differentiate. The structure and distribution of Jeb protein implies that Jeb functions as a signal to organize the development of visceral muscles. Here we show that the Jeb receptor is the Drosophila homologue of anaplastic lymphoma kinase (Alk), a receptor tyrosine kinase of the insulin receptor superfamily. Human ALK was originally identified as a proto-oncogene, but its normal function in mammals is not known. In Drosophila, localized Jeb activates Alk and the downstream Ras/mitogen-activated protein kinase cascade to specify a select group of visceral muscle precursors as muscle-patterning pioneers. Jeb/Alk signalling induces the myoblast fusion gene dumbfounded (duf; also known as kirre) as well as org-1, a Drosophila homologue of mammalian TBX1, in these cells.
authors.affiliation: Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1020, New York, New York 10029, USA.
authors.forename: Hsiu-Hsiang
authors.initials: HH
authors.lastname: Lee
authors.forename: Audra
authors.initials: A
authors.lastname: Norris
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Weiss
authors.forename: Manfred
authors.initials: M
authors.lastname: Frasch
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009124:Muscle Proteins; D009132:Muscles / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D020794:Receptor Protein-Tyrosine Kinases; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D000090063:Proto-Oncogene Mas; D020825:T-Box Domain Proteins; C440828:jeb protein, Drosophila; C413082:kirre protein, Drosophila; C117917:org-1 protein, Drosophila; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases