Characterization of the Drosophila nonreceptor tyrosine kinase DACK and its role in Dcdc42 signaling. N. Harden ¹, K. Sem ¹, L. Lim ^2,3. 1) Dept Molec Biol & Biochem, Simon Fraser Univ, Burnaby, BC, Canada; 2) Institute of Molecular and Cell Biology, Singapore; 3) Institute of Neurology, London, UK.

   The Ras-related small GTPase Cdc42 participates in a wide range of cellular events including regulation of the actin cytoskeleton and signaling through the Jun N-terminal kinase (JNK) pathway. The mammalian nonreceptor tyrosine kinase ACK was originally identified as a binder of active, GTP-bound Cdc42 and is a likely downstream effector. We are characterizing a Drosophila homolog of ACK, DACK, as part of our study of Drosophila Cdc42 (Dcdc42) signaling during development. Expression of a kinase-dead DACK transgene at various times during development has similar phenotypic effects as loss of Dcdc42 signaling, including disruption of dorsal closure. Overexpression of wild-type DACK can rescue the dorsal closure defect caused by expression of dominant negative Dcdc42, indicating that DACK is a Dcdc42 effector during morphogenesis of the epidermis. Unlike mammalian ACK, DACK does not bind to Cdc42, but does show a tissue-specific transcriptional response to changes in Dcdc42 signaling. We are interested in finding targets for DACK and are currently using a rough eye phenotype induced by DACK overexpression to screen for second-site modifiers.