cDNA cloning of the rat IGF I receptors: structural analysis of rat and human IGF I and insulin receptors reveals differences in alternative splicing and receptor-specific domain conservation.
IGF I and insulin receptors are homologous proteins that function in distinct physiological pathways. To define domains that might contribute to differences between IGF I and insulin receptors, we cloned the rat IGF I receptor cDNA and performed a comparative sequence analysis of specific functional domains in the two receptor types of rats and humans. Since alternative splicing has been shown to alter the activities of both IGF I and insulin receptors, we also examined the mRNA splicing patterns of the two receptors. The C-terminal region exhibits the lowest degree of amino acid homology between rat and human IGF I receptors (85%) and the tyrosine kinase domain the highest homology (98%). In the region corresponding to the CAG+/-alternative splicing site of the human IGF I receptor, a nucleotide change in the rat eliminates the alternative acceptor splice site. The rat IGF I receptor has no equivalent to the alternatively spliced exon 11 of the insulin receptor. The IGF I and insulin receptors are highly homologous in the tyrosine kinase domain (84%), but differ markedly in other specific regions (e.g., 22-26% homology in the transmembrane domain, 45% homology in the C-terminal domain). We speculate that these regions of divergent sequence may have roles in determining distinct signaling properties of IGF I and insulin receptors.
Pedrini
M T
MT
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215.
Giorgino
F
F
Smith
R J
RJ
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics*; D005091:Exons; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000235:genetics*; D011972:Receptor, Insulin / Q000737:chemistry / Q000235:genetics*; D017385:Sequence Homology
D018076:DNA, Complementary; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin