A NOVEL DROSOPHILA RECEPTOR TYROSINE KINASE EXPRESSED SPECIFICALLY INTHE NERVOUS-SYSTEM - UNIQUE STRUCTURAL FEATURES AND IMPLICATION IN DEVELOPMENTAL SIGNALING

We report the identification and characterization of Dnrk (Drosophila neurospecific receptor kinase), a Drosophila gene encoding a putative receptor tyrosine kinase (RTK) highly related to the Trk and Ror famil ies of RTKs. During Drosophila embryogenesis, the Dnrk gene is express ed specifically in the developing nervous system. The Dnrk protein pos sesses two conserved cysteine-containing domains and a kringle domain within its extracellular domain, resembling those observed in Ror fami ly RTKs (Ror1, Ror2, and a Drosophila Ror, Dror). This protein contain s the catalytic tyrosine kinase (TK) domain with two putative ATP bind ing motifs, resembling those observed in another Drosophila RTK (Dtrk) that mediates hemophilic cell adhesion. The TK domain of Dnrk, expres sed in bacteria or mammalian cells, exhibits apparent autophosphorylat ion activities in vitro. The TK domain lacking the distal ATP-binding motif also exhibits autophosphorylation activity, yet to a lesser exte nt. In addition to its TK activity, there are several putative tyrosin e-containing motifs that upon phosphorylation may interact with Src ho mology 2 regions of other signaling molecules. Collectively, these res ults suggest that Dnrk may play an important role in neural developmen t during Drosophila embryogenesis.