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

Abstract

The Drosophila gene Dstpk61 encodes a serine threonine protein kinase homologous to human phosphoinositide-dependent protein kinase (PDK1), and also has homologues in S. cerevisiae, S. pombe, C. elegans, A. thaliana, mouse, and sheep. Where its function has been investigated, this kinase is thought to be involved in regulating cell growth and survival in response to extracellular signals such as insulin and growth factors. In Drosophila it produces multiple transcripts, some of which appear to be sex-specific. In addition to the five Dstpk6I cDNAs we have described previously we report the existence of a further 18 expressed sequence tag (EST) cDNAs, three of which we have fully sequenced. We conclude that Dstpk6I is a complex locus that utilises a combination of alternative promoters, alternative splice sites and alternative polyadenylation sites to produce a vast array of different transcripts. These cDNAs encode at least four different DSTPK61 protein isoforms with variant N-termini. In this paper, we discuss the possible functions of the distinct Dstpk6I transcripts and how they might be differentially regulated. We also discuss the roles that DSTPK61 protein isoforms might play in relation tO the protein domains they contain and their potential targets in the cell. Finally, we report the putative structure of the human PDK1 gene based on computer comparisons of available mRNA and genomic sequences. The value of using sequence data from other species for experimental design in mammalian systems is discussed.