FUNCTIONAL DOMAINS OF FUSED, A SERINE THREONINE KINASE REQUIRED FOR SIGNALING IN DROSOPHILA

fused (fu) is a segment-polarity gene encoding a putative serine-threo nine kinase. In a wild-type context, all Su mutations display the same set of phenotypes. Nevertheless, mutations of the Suppressor of fused [Su(fu)] gene define three classes of alleles (fuO, fuI, fuII). Here, we report the molecular analysis of known fu mutations and the genera tion of new alleles by in vitro mutagenesis. We show that the Fused (F u) protein functions in vitro as a kinase. The N-terminal kinase and t he extreme C-terminal domains are necessary for Fu(+) activity while a central region appears to be dispensable. We observe a striking corre lation between the molecular lesions of fu mutations and the phenotype displayed in their interaction with Su(fu). Indeed, fuI alleles which are suppressed by Su(fu) mutations are defined by in frame alteration s of the N-terminal catalytic domain whereas the C-terminal domain is missing or altered in all fuII alleles. An unregulated Full protein, w hich can be limited to the 80 N-terminal amino acids of the kinase dom ain, would be responsible for the neomorphic costal-2 phenotype displa yed by the fuII-Su(fu) interaction. We propose that the Fu C-terminal domain can differentially regulate the Fu catalytic domain according t o cell position in the parasegment.