The Drosophila Insulin Receptor Contains a Novel Carboxyl-terminal Extension Likely to Play an Important Role in Signal Transduction (*)
- From the Department of Anatomy and Cell Biology, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York 11203
- § To whom reprint requests and correspondence should be addressed. Tel.: 718-270-1060; Fax: 718-270-3732. The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) U18351[GenBank].
Abstract
The nucleic acid and deduced amino acid sequence of the Drosophila insulin receptor homologue (dir) has been determined. The coding sequence of dir is contained within 10 exons spanning less than 8 kilobase pairs 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 amino acid identity between the DIR and human insulin and insulin-like growth factor-I receptors is 32.5 and 33.3%, respectively. Higher levels of identity are found in exon 2 (45 and 43%, respectively) and in the β subunit (50 and 48%, respectively), and the positions of most cysteine residues in the α subunit cysteine-rich domain are conserved. A novel, 400-amino acid, carboxyl-terminal extension contains 9 tyrosine residues, four of which are present in YXXM or YXXL motifs, suggesting that they function as binding sites for SH2 domain-containing signaling proteins. The presence of multiple putative SH2 domain binding sites in the DIR represents a significant difference from its mammalian homologues and suggests that, unlike the human insulin and insulin-like growth factor-I receptors, the DIR forms stable complexes with signaling molecules as part of its signal transduction mechanism.
Footnotes
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↵* This work was supported by Grant IBN 92-13992 from the National Science Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- IGF
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insulin-like growth factor
- kb
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kilobase pair(s)
- PCR
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polymerase chain reaction
- IRS-1
-
insulin receptor substrate 1.
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↵2M. Marin-Hincapie and R. S. Garofalo, unpublished observations.
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- Received October 20, 1994.
- Revision received December 12, 1994.
