Generation. of a novel A kinase anchor protein and a myristoylated alanine-rich C kinase substrate-like analog from a single gene

A unique Drosophila gene encodes two novel signaling proteins. Drosophila A kinase anchor protein 200 (DAKAP200) (753 amino acids) binds regulatory su bunits of protein kinase All (PKAII) isoforms in vitro and in intact cells. The acidic DAKAP200 polypeptide (pI similar to 3.8) contains an optimal N- terminal myristoylation site and a positively charged domain that resembles the mul tifunctional phosphorylation site domain of vertebrate myristoylat ed alanine-rich C kinase substrate proteins. The 15-kilobase pair DAHAP200 gene contains six exons and encodes a second protein, Delta DAKAP200. Delta DAKAP200 is derived from DAKAP200 transcripts by excision of exon 5 (381 c odons), which encodes the PKAII binding region and a Pro-rich sequence. Del ta DAKAP200 appears to be a myristoylated alanine-rich C kinase substrate a nalog. DAKAP200 and Delta DAKAP200 are evident in vivo at all stages of Dro sophila development. Thus, both proteins may play important physiological r oles throughout the life span of the organism. Nevertheless, DAKAP200 gene expression is regulated. Maximal levels of DAKAP200 are detected in the pup al phase of development; Delta DAKAP200 content is elevated 7-fold in adult head (brain) relative to other body parts. Enhancement or suppression of e xon 5 excision during DAKAP200 pre-mRNA processing provides potential mecha nisms for regulating anchoring of PKAII and targeting of cAMP signals to ef fector sites in cytoskeleton and/or organelles.