Home LiteratureArticle Details
PMID: 2877871 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.

The EMBO journal ·Vol. 5 ·No. 10 ·1986-10-00 ·Pages 2503-12

Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E

Abstract

To identify structural characteristics of the closely related cell surface receptors for insulin and IGF-I that define their distinct physiological roles, we determined the complete primary structure of the human IGF-I receptor from cloned cDNA. The deduced sequence predicts a 1367 amino acid receptor precursor, including a 30-residue signal peptide, which is removed during translocation of the nascent polypeptide chain. The 1337 residue, unmodified proreceptor polypeptide has a predicted Mr of 151,869, which compares with the 180,000 Mr IGF-I receptor precursor. In analogy with the 152,784 Mr insulin receptor precursor, cleavage of the Arg-Lys-Arg-Arg sequence at position 707 of the IGF-I receptor precursor will generate alpha (80,423 Mr) and beta (70,866 Mr) subunits, which compare with approximately 135,000 Mr (alpha) and 90,000 Mr (beta) fully glycosylated subunits.

MeSH Terms
Amino Acid Sequence Base Sequence Chromosome Mapping Cloning, Molecular DNA/analysis Female Humans Placenta/metabolism Poly A/genetics Pregnancy RNA, Messenger/genetics Receptor, Insulin/genetics,isolation & purification,metabolism Receptors, Somatomedin Sequence Homology, Nucleic Acid
Chemicals
RNA, Messenger Receptors, Somatomedin Poly A DNA Receptor, Insulin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Ullrich A
Gray A
Tam A W
Yang-Feng T
Tsubokawa M
Collins C
Henzel W
Le Bon T
Kathuria S
Chen E
References (50)
50 references, click to expand
  1. The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling.
    Cell. 1985 Apr;40(4):747-58 PMID: 2859121
  2. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes.
    Nature. 1985 Feb 28-Mar 6;313(6005):756-61 PMID: 2983222
  3. The nature and regulation of the receptors for insulin-like growth factors.
    Annu Rev Physiol. 1985;47:425-42 PMID: 2986537
  4. Actions of insulin-like growth factors.
    Annu Rev Physiol. 1985;47:443-67 PMID: 2986538
  5. Assignment of the human 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible cytochrome P1-450 gene to chromosome 15.
    Nucleic Acids Res. 1985 Mar 25;13(6):2009-16 PMID: 4000952
  6. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1.
    Cell. 1985 Jul;41(3):665-76 PMID: 2408759
  7. Protein kinase C phosphorylates pp60src at a novel site.
    Cell. 1985 Oct;42(3):849-57 PMID: 2996780
  8. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
    Science. 1985 Dec 6;230(4730):1132-9 PMID: 2999974
  9. A cytochrome P-450 gene family mapped to human chromosome 19.
    Ann Hum Genet. 1985 Oct;49(Pt 4):267-74 PMID: 3000277
  10. Receptor aggregation is necessary for activation of the soluble insulin receptor kinase.
    J Biol Chem. 1986 Jan 15;261(2):889-94 PMID: 3510209
  11. Phosphorylation of receptors for insulin and insulin-like growth factor I. Effects of hormones and phorbol esters.
    J Biol Chem. 1986 Jan 15;261(2):934-9 PMID: 3001088
  12. The pronatriodilatin gene is located on the distal short arm of human chromosome 1 and on mouse chromosome 4.
    Am J Hum Genet. 1985 Nov;37(6):1117-28 PMID: 2934979
  13. Urea treatment allows dithiothreitol to release the binding subunit of the insulin receptor from the cell membrane: implications for the structural organization of the insulin receptor.
    Biochem Biophys Res Commun. 1985 Dec 17;133(2):389-96 PMID: 4084284
  14. Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts.
    Proc Natl Acad Sci U S A. 1986 Feb;83(3):664-8 PMID: 3003744
  15. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus.
    Nature. 1986 Mar 20-26;320(6059):277-80 PMID: 2421165
  16. Purification of insulin-like growth factor I receptor from human placental membranes.
    J Biol Chem. 1986 Jun 15;261(17):7685-9 PMID: 3011795
  17. Confirmation of the synteny of the human genes for mannose phosphate isomerase and pyruvate kinase and of their assignment to chromosome 15.
    Cytogenet Cell Genet. 1975;15(5):299-305 PMID: 1222586
  18. Efficeint transcription of RNA into DNA by avian sarcoma virus polymerase.
    Biochim Biophys Acta. 1976 Sep 6;442(3):324-30 PMID: 183818
  19. Expression of alpha-D-mannosidase in man-hamster somatic cell hybrids.
    Biochem Genet. 1977 Jun;15(5-6):455-76 PMID: 880209
  20. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination.
    Biochemistry. 1977 Oct 18;16(21):4743-51 PMID: 911786
  21. Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells.
    J Biol Chem. 1978 Oct 25;253(20):7570-8 PMID: 81205
  22. Regulation of insulin receptors and insulin responsiveness in 3T3-L1 fatty fibroblasts.
    Endocrinology. 1979 May;104(5):1383-92 PMID: 436783
  23. Assignment of cytoplasmic alpha-mannosidase (MANA) and confirmation of mitochondrial isocitrate dehydrogenase (IDHM) to the q11 leads to qter region of chromosome 15 in man.
    Cytogenet Cell Genet. 1978;22(1-6):498-502 PMID: 752528
  24. Requirement of human chromosomes 19, 6 and possibly 3 for infection of hamster x human hybrid cells with baboon M7 type C virus.
    Cell. 1979 Sep;18(1):135-43 PMID: 228859
  25. Synthesis of oligonucleotides on cellulose by a phosphotriester method.
    Nucleic Acids Res. 1980 May 24;8(10):2331-48 PMID: 7433092
  26. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization.
    Chromosoma. 1981;83(3):431-9 PMID: 7273954
  27. Somatomedin receptor of human placenta: solubilization, photolabeling, partial purification, and comparison with insulin receptor.
    Proc Natl Acad Sci U S A. 1981 Jul;78(7):4279-83 PMID: 6270667
  28. Structural similarities between human receptors for somatomedin C and insulin: analysis by affinity labeling.
    Biochemistry. 1981 Dec 22;20(26):7345-50 PMID: 6275879
  29. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor.
    J Biol Chem. 1982 May 10;257(9):5038-45 PMID: 6279656
  30. A simple method for displaying the hydropathic character of a protein.
    J Mol Biol. 1982 May 5;157(1):105-32 PMID: 7108955
  31. Monensin blocks the maturation of receptors for insulin and somatomedin C: identification of receptor precursors.
    Proc Natl Acad Sci U S A. 1983 Mar;80(5):1228-31 PMID: 6298786
  32. Purification of insulin receptor with full binding activity.
    J Biol Chem. 1983 Apr 25;258(8):5045-9 PMID: 6833291
  33. Monoclonal antibodies to receptors for insulin and somatomedin-C.
    J Biol Chem. 1983 May 25;258(10):6561-6 PMID: 6304046
  34. Isolation of microgram quantities of proteins from polyacrylamide gels for amino acid sequence analysis.
    Methods Enzymol. 1983;91:227-36 PMID: 6855576
  35. Chromosomal sublocalization of human c-myb and c-fes cellular onc genes.
    Nature. 1983 Jul 14-20;304(5922):169-71 PMID: 6866112
  36. Somatomedin-C stimulates the phosphorylation of the beta-subunit of its own receptor.
    J Biol Chem. 1983 Aug 25;258(16):9581-4 PMID: 6309774
  37. Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor I.
    Nature. 1983 Sep 29-Oct 5;305(5933):438-40 PMID: 6312321
  38. Phorbol esters stimulate the phosphorylation of receptors for insulin and somatomedin C.
    Proc Natl Acad Sci U S A. 1983 Oct;80(20):6211-3 PMID: 6312447
  39. A method for isolation of intact, translationally active ribonucleic acid.
    DNA. 1983;2(4):329-35 PMID: 6198133
  40. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs.
    Nucleic Acids Res. 1984 Jan 25;12(2):857-72 PMID: 6694911
  41. Insulin-like growth factor-I (IGF-I) stimulates tyrosine kinase activity in purified receptors from a rat liver cell line.
    Biochem Biophys Res Commun. 1984 Feb 29;119(1):6-13 PMID: 6322788
  42. Role of glycosylation in the processing of newly translated insulin proreceptor in 3T3-L1 adipocytes.
    J Biol Chem. 1984 Apr 10;259(7):4566-75 PMID: 6368559
  43. Isolation of the human insulin-like growth factor I gene using a single synthetic DNA probe.
    EMBO J. 1984 Feb;3(2):361-4 PMID: 6232133
  44. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells.
    Nature. 1984 May 31-Jun 6;309(5967):418-25 PMID: 6328312
  45. A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids.
    Anal Biochem. 1984 Apr;138(1):141-3 PMID: 6731838
  46. Protein kinase C phosphorylation of the EGF receptor at a threonine residue close to the cytoplasmic face of the plasma membrane.
    Nature. 1984 Oct 4-10;311(5985):480-3 PMID: 6090944
  47. The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA.
    Cell. 1984 Nov;39(1):27-38 PMID: 6091915
  48. Phorbol esters modulate insulin receptor phosphorylation and insulin action in cultured hepatoma cells.
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7797-801 PMID: 6393128
  49. Nucleotide sequence of avian sarcoma virus UR2 and comparison of its transforming gene with other members of the tyrosine protein kinase oncogene family.
    J Virol. 1985 Mar;53(3):879-84 PMID: 2983097
  50. Gene for human insulin receptor: localization to site on chromosome 19 involved in pre-B-cell leukemia.
    Science. 1985 May 10;228(4700):728-31 PMID: 3873110
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1986-10-00
Pages
2503-12
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1167146
Subset
IM
Grants
NIADDK NIH HHS · AM29770 · United States
NIADDK NIH HHS · AM34427 · United States
NCI NIH HHS · CA-16417 · United States
Databases
GENBANK
M24599
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2