ISOLATION OF A RECEPTOR TYROSINE KINASE (DTK) FROM EMBRYONIC STEM-CELLS - STRUCTURE, GENETIC-MAPPING AND ANALYSIS OF EXPRESSION

Analysis of receptor tyrosine kinases expressed during mouse embryonic stem cell differentiation resulted in the cloning of a receptor desig nated developmental tyrosine kinase (DTK). The 850 amino acid mature r eceptor protein comprises an extracellular domain with two immunoglobu lin-like motifs and two fibronectin type III modules, a 25 amino acid transmembrane domain and a cytoplasmic region with a catalytic kinase domain. In embryonic stem cells growing in the presence of leukemia in hibitory factor DTK is abundantly expressed, and this level of express ion is maintained in differentiating embryonic stem cells and cystic e mbryoid bodies. In mid-gestational embryos (E14.5), DTK RNA is express ed in many tissues including brain, eye, thymus, lung, heart, gut, liv er, testis and limbs. In contrast, expression of DTK in adult mice bec omes restricted to brain, portions of the gastrointestinal tract, blad der, testis and ovary. There is enrichment of transcripts encoding DTK in purified fetal liver hematopoietic stem cells, when compared with unfractionated fetal liver. The DTK gene maps to mouse chromosome 2, b and F.