The derailed guidance receptor does not require kinase activity in vivo.

The Drosophila Derailed (DRL) receptor tyrosine kinase (RTK) controls key guidance events in the developing nervous system and mesoderm. Like other members of the "related to tyrosine kinases" (RYK) subfamily of RTKs, DRL has several highly unusual amino acid substitutions within the catalytic domain, raising the possibility that members of this subfamily are catalytically inactive. To test the role of DRL kinase activity in vivo, we mutated the invariant lysine required for catalytic activity of known kinases and examined the ability of this mutant to function in two assays: a dominant gain-of-function axon switch assay in the nervous system and phenotypic rescue of muscle attachment in drl mutants. We show that this predicted kinase-deficient DRL mutant is capable of functioning in both assays. Our results indicate that DRL does not require kinase activity in vivo and suggest that members of the RYK subfamily of RTKs transduce signals unconventionally.