Evidence for two insulin-like growth factor I receptors with distinct primary structure that are differentially expressed during development.
We have previously presented evidence for two IGF I receptor species in rat skeletal muscle. One form of IGF I receptor is selectively expressed in fetal and early postnatal life, and the second is present in both fetal and adult animals. These two IGF I receptors were shown to have similar tryptic phosphopeptide maps but to differ in beta subunit molecular weight (105,000 for the fetal vs. 95,000 for the adult type receptor). In this study, we have used specific antibodies to investigate the structural relationships between the two IGF I receptors. Anti-IGF I receptor beta subunit antibodies were generated against synthetic peptides corresponding to residues 1284-1293 and 1308-1318 of the cloned human IGF I receptor, and the capacity of these antibodies to interact with the two IGF I receptors was investigated. Both anti-peptide antibodies selectively immunoprecipitated the higher molecular weight fetal receptor and not the adult receptor from rat muscle. Human placenta and muscle were shown to contain two receptors similar to those observed in rat muscle. In human muscle, the anti-peptide antibodies and the human-specific monoclonal alpha subunit antibody alpha-IR3 also selectively immunoprecipitated the fetal type receptor. The presence of a 95,000 M(r) IGF I receptor beta subunit distinct from the insulin receptor beta subunit in human muscle was confirmed by the demonstration of an IGF I sensitive receptor with a beta subunit of this size after insulin receptor immunodepletion. These data strongly support the conclusion that the fetal and adult type IGF I receptors differ in primary structure. The fetal receptor corresponds to the cloned and sequenced IGF I receptor, and the primary structure of the adult type receptor has not yet been established.
Alexandrides
T K
TK
Elliott P. Joslin Research Laboratory, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215.
Chen
J H
JH
Bueno
R
R
Giorgino
F
F
Smith
R J
RJ
D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D005314:Embryonic and Fetal Development; D005260:Female; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D024510:Muscle Development; D009132:Muscles / Q000196:embryology / Q000378:metabolism*; D010449:Peptide Mapping; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010748:Phosphopeptides / Q000032:analysis; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism
D000906:Antibodies; D046911:Macromolecular Substances; D010455:Peptides; D010748:Phosphopeptides; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1