Protein phosphorylation plays an essential role in the regulation of alternative splicing and sex determination in Drosophila

Alternative mRNA splicing directed by SR proteins and the splicing regulato rs TRA and TRAP is an essential feature of Drosophila sex determination. Th ese factors are highly phosphorylated, but the role of their phosphorylatio n in vivo is unclear. We show that mutations in the Drosophila LAMMER kinas e, Doa, alter sexual differentiation and interact synergistically with ba a nd tra2 mutations, Doa mutations disrupt sex-specific splicing of doublesex pre-mRNA, a key regulator of sex determination, by affecting the phosphory lation of one or more proteins in the female-specific splicing enhancer com plex. Examination of pre-mRNAs regulated similarly to dsx shows that the re quirement for Das is substrate specific. These results demonstrate that a S R protein kinase plays ii specific role In developmentally regulated altern ative splicing.