Jeb and Alk Pair Up

Abstract

Jelly belly (Jeb), a protein required for Drosophila visceral muscle development, has had no known receptor; the proto-oncogene anaplastic lymphoma kinase (Alk) is a receptor tyrosine kinase whose normal function had not been identified (see Freeman). Research from two groups converged to show that, in Drosophila , Jeb signals through Alk and is critical for the formation of founder cells, which establish visceral muscles and recruit myoblasts to fuse with them and to form muscle fibers. Lee et al. used genetic analysis in combination with immunostaining, in situ hybridization, cell-lineage experiments, and reporter gene expression to show that Jeb, signaling through the Ras mitogen-activated protein kinase (MAPK) pathway, stimulated or repressed appropriate target genes to specify founder cell formation. Flies with deficient Alk activity (through mutation, expression of dominant-negative Alk, or RNA interference) had phenotypes similar to those of jeb mutants. Moreover, Jeb bound to mammalian tissue culture cells transfected with Alk and activated the MAPK cascade. Englund et al. , noting that mutant Alk and jeb larvae lack intestines, analyzed visceral mesoderm development in wild-type and mutant flies. The authors used immunostaining and in situ hybridization to implicate Jeb and Alk in activation of extracellular signal-regulated kinase and expression of a target gene required for muscle fusion. Englund et al. showed that, whereas Jeb binding depended on the Alk extracellular domain, its subsequent internalization and degradation required Alk tyrosine kinase activity. Identification of Alk as a Jeb receptor will likely facilitate the identification of receptors for related signaling molecules; the relation between the physiological function of Alk and its oncogenic potential remains to be defined. H.-H. Lee, A. Norris, J. B. Weiss, M. Frasch, Jelly belly protein activates the receptor tyrosine kinase Alk to specify visceral muscle pioneers. Nature 425 , 507-512 (2003). [Online Journal] C. Englund, C. E. Lorén, C. Grabbe, G. K. Varshney, F. Deleuil, B. Hallberg, R. H. Palmer, Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion. Nature 425 , 512-516 (2003). [Online Journal] M. Freeman, Partners united, Nature 425 , 468-469 (2003). [Online Journal]