The Dstpk61 locus of Drosophila produces multiple transcripts and protein isoforms, suggesting it is involved in multiple signalling pathways

The Drosophila gene Dstpk61 encodes a serine threonine protein kinase homol ogous to human phosphoinositide-dependent protein kinase (PDK1), and also h as homologues in S. cerevisiae, S. pombe, C, elegans, A. thaliana, mouse, a nd sheep. Where its function has been investigated, this kinase is thought to be involved in regulating cell growth and survival in response to extrac ellular signals such as insulin and growth factors. In Drosophila produces multiple transcripts, some of which appear to be sex-specific. In addition to the five Dstpk61 cDNAs we have described previously we repor t the existence of a further 18 expressed sequence tag (EST) cDNAs, three o f which we have fully sequenced. We conclude that Dstpk61 is a complex locu s that utilises a combination of alternative promoters, alternative splice sites and alternative polyadenylation sites to produce a vast array of diff erent transcripts. These cDNAs encode at least four different DSTPK61 prote in isoforms with variant N-termini. In this paper, we discuss the possible functions of the distinct Dstpk61 transcripts and how they might be differe ntially regulated. We also discuss the roles that DSTPK61 protein isoforms might play in relation to the protein domains they contain and their potent ial targets in the cell. Finally, we report the putative structure of the h uman PDK1 gene based on computer comparisons of available mRNA and genomic sequences. The value of using sequence data from other species for experime ntal design in mammalian systems is discussed.