DEVELOPMENTAL REGULATION OF EXPRESSION AND ACTIVITY OF MULTIPLE FORMS OF THE DROSOPHILA RAC PROTEIN-KINASE

We have characterized the Drosophila homologue of the proto-oncogenic RAG protein kinase (DRAG-PH). The DRAG-PH gene gives rise to two transcripts with the same coding potential, generated by the use of two different polyadenylation signals. Each transcript encodes two polypeptides because of the presence of a weaker initiator ACG codon, upstream hom the major AUG, such that the larger protein contains an N-terminal extension. Like the human isoforms, DRAC-PKs possess a novel signaling region, the pleckstrin homology domain. DRAG-PH proteins have a similar expression pattern, being regulated both maternally and zygotically, and are expressed throughout Drosophila development. Antisera specific for recombinant DRAG-PR and for its C terminus detected two polypeptides of 66 and 85 kDa in Drosophila extracts. The antirecombinant antisera also recognized a polypeptide of 120 kDa from Drosophila, which apparently shared an epitope related to DRAG-PH sequences. The role of p120 appears to be restricted compared with that of DRAG-PH, since it was not detected in larvae or adult flies. There was no spatial restriction of DRAG-PH expression during embryogenesis, suggesting that localized activation might be a regulatory mechanism for its function. DRAG-PH possesses an intrinsic kinase activity that is similar to 8-fold higher in adult flies than in 0-3-h embryos undergoing rapid mitotic cycles.