BOTH SYNCHRONOUS AND ASYNCHRONOUS MUSCLE ISOFORMS OF PROJECTIN (THE DROSOPHILA BENT LOCUS PRODUCT) CONTAIN FUNCTIONAL KINASE DOMAINS

In Drosophila, the large muscle protein, projectin, has very different localizations in synchronous and asynchronous muscles, suggesting tha t projectin has different functions in different muscle types. The mul tiple projectin isoforms are encoded by a single gene; however they di ffer significantly in size (as detected by gel mobility) and show diff erences in some peptide fragments, presumably indicating alternative s plicing or termination. We now report additional sequence of the proje ctin gene, showing a kinase domain and flanking regions highly similar to equivalent regions of twitchin, including a possible autoinhibitor y region. In spite of apparent differences in function, all isoforms o f projectin have the kinase domain and all are capable of autophosphor ylation in vitro. The projectin gene is in polytene region 102C/D wher e the bent(D) phenotype maps. The recessive lethality of bent(D) is as sociated with a breakpoint that removes sequence of the projectin kina se domain. We find that different alleles of the highly mutable recess ive lethal complementation group, l(4)2, also have defects in differen t parts of the projectin sequence, both NH2-terminal and COOH-terminal to the bent(D) breakpoint. These alleles are therefore renamed as all eles of the bent locus. Adults heterozygous for projectin mutations sh ow little, if any, effect of one defective gene copy, but homozygosity for any of the defects is lethal. The times of death can vary with al lele. Some alleles kill the embryos, others are larval lethal. These m olecular studies begin to explain why genetic studies suggested that l (4)2 was a complex (or pseudoallelic) locus.