Program Nr: 402

A role for DAlk, a novel Drosophila RTK, in the development of the visceral mesoderm. R.H. Palmer 1, A. Scully 2, J. Thomas 2, M. McKeown 2, T. Hunter 2, C.E. Loren 1. 1) UCMP, Umea University, Umea, Sweden; 2) Salk Institute, 10010N. Torrey Pines Road, La Jolla, CA 92037-1099, USA.

   In humans, one third of non-Hodgkins lymphomas involve a 2;5 chromosomal translocation. In this translocation the catalytic domain of the orphan RPTK ALK is fused to a nuclear phosphoprotein: NPM (nucleophosmin) producing a NPM-ALK/p80 protein with constituative PTK activity. This NPM-ALK/p80 fusion protein is capable of transformation when expressed in several cell lines. We have identified a Drosophila melanogaster homologue of the HsALK RPTK. We have named this DAlk. DAlk shows homology to the orphan RPTKs, HsALK and HsLTK, in the extracellular domain as well as general high homology with the intracellular domain of RPTKs of the Insulin receptor superfamily. DmALK encodes a 220kDa protein which is tyrosine phosphorylated and localises to the plasma membrane of cells. In situ hybridisation analysis using DAlk mRNA shows that it is expressed in the mesoderm and CNS of developing embryos. Using the GAL4-UAS inducible system we have created transgenic flies expressing DAlk wild-type, activated and dominant-negative proteins. The results of these in vivo analyses will be described and discussed. This work was supported by the Human Frontiers Science Programme, NIH grants CA39780 and MH57460, and the Svenska Sllskapet fr Medicinsk Forskning.
   
   
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