THE DROSOPHILA INSULIN-RECEPTOR CONTAINS A NOVEL CARBOXYL-TERMINAL EXTENSION LIKELY TO PLAY AN IMPORTANT ROLE IN SIGNAL-TRANSDUCTION

The nucleic acid and deduced amino acid sequence of the Drosophila ins ulin receptor homologue (dir) has been determined, The coding sequence of dir is contained within 10 exons spanning less than 8 kilobase pai rs of genomic DNA. The deduced amino acid sequence of the dir encodes a protein of 2148 amino acids, larger than the human insulin receptor due to amino- and carboxyl-terminal extensions, The overall level of a mino acid identity between the DIR and human insulin and insulin like growth factor-I receptors is 32.5 and 33.3%, respectively, Higher leve ls of identity are found in exon 2 (45 and 43%, respectively) and in t he beta subunit (50 and 48%, respectively), and the positions of most cysteine residues in the ct subunit cysteine rich domain are conserved , A novel, 400-amino acid, carboxyl-terminal extension contains 9 tyro sine residues, four of which are present in YXXM or YXXL motifs, sugge sting that they function as binding sites for SH2 domain-containing si gnaling proteins, The presence of multiple putative SH2 domain binding sites in the DIR represents a significant difference from its mammali an homologues and suggests that, unlike the human insulin and insulinl ike growth factor-I receptors, the DIR forms stable complexes with sig naling molecules as part of its signal transduction mechanism.