Structure and function of the insulin receptor-a personal perspective
Open accessAbstract
Immunoprecipitation with autoantibodies to the insulin receptor derived from patients with extreme insulin resistance and acanthosis nigricans revealed that the receptor is comprised of two subunits of 135 kDa (α subunit) and 95 kDa (β subunit) and that insulin induces the rapid phosphorylation of the β subunit in intact cells. Incubation of a highly purified insulin receptor preparation with [γ-32P]ATP also resulted in tyrosine phosphorylation of the β subunit in an insulin-dependent manner, suggesting that the receptor itself is a tyrosine-specific protein kinase. Furthermore, a Japanese boy with insulin resistance and acanthosis nigricans was found to be heterozygous for a mutation of the insulin receptor gene that resulted in the replacement of glycine-996 with valine in the ATP binding site of the receptor. Expression of the mutant receptor in cultured cells revealed it to be deficient in tyrosine kinase activity and mediation of insulin action, suggesting that the tyrosine kinase activity of the insulin receptor is essential for insulin action in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Any impairments occur on main phosphorylation sites will reduce insulin receptor tyrosine kinase activity, eventually affecting the insulin function.
“Therefore, any impairments occur on main phosphorylation sites will reduce insulin receptor tyrosine kinase activity, eventually affecting the insulin function (88–90).”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [89]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Transforming gene product of Rous sarcoma virus phosphorylates tyrosine
Hunter, T. R., & Sefton, B. M. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.3.1311 · Cited by 2,333 · see citing works
Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes
Ullrich, A., Bell, J. R., Chen, E. Y., Herrera, R., Petruzzelli, L., Dull, T. J., Gray, A., Coussens, L. M., Liao, Y.-C., Tsubokawa, M., et al. (1985) · Nature · doi:10.1038/313756a0 · Cited by 2,251 · see citing works
The human insulin receptor cDNA: The structural basis for hormone-activated transmembrane signalling
Ebina, Y., Ellis, L., Jarnagin, K., Edery, M., Gráf, L., Clauser, É., Ou, J. J., Masiarz, F. R., Kan, Y. W., Goldfine, I. D., et al. (1985) · Cell · doi:10.1016/0092-8674(85)90334-4 · Cited by 1,477 · see citing works
Ushiro, H., & Cohen, S. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43497-7 · Cited by 1,184 · see citing works
Insulin Stimulates the Phosphorylation of the 95,000-Dalton Subunit of Its Own Receptor
Kasuga, M., Karlsson, F. A., & Kahn, C. R. (1982) · Science · doi:10.1126/science.7031900 · Cited by 1,132 · see citing works
Self-citationInsulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system
Kasuga, M., Zick, Y., Blithe, D., Crettaz, M., & Kahn, C. R. (1982) · Nature · doi:10.1038/298667a0 · Cited by 680 · see citing works
Self-citationStimulation of tyrosine-specific phosphorylation by platelet-derived growth factor
Ek, B., Westermark, B., Wasteson, Å., & Heldin, C. (1982) · Nature · doi:10.1038/295419a0 · Cited by 658 · see citing works
Chou, C. K., Dull, T. J., Russell, D. S., Gherzi, R., Lebwohl, D., Ullrich, A., & Rosen, O. M. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)75716-0 · Cited by 640 · see citing works
Collett, M. S., Purchio, A. F., & Erikson, R. L. (1980) · Nature · doi:10.1038/285167a0 · Cited by 505 · see citing works
Freychet, P., Roth, J., & Neville, D. M. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.8.1833 · Cited by 500 · see citing works
Insulin-Receptor Interactions in Adipose Tissue Cells: Direct Measurement and Properties
Cuatrecasas, P. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.6.1264 · Cited by 441 · see citing works
Flier, J. S., Kahn, C. R., Roth, J., & Bar, R. S. (1975) · Science · doi:10.1126/science.170678 · Cited by 438 · see citing works
Kasuga, M., Zick, Y., Blith, D. L., Karlsson, F., Häring, H.-U., & Kahn, C. R. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33955-3 · Cited by 437 · see citing works
Self-citationInsulin-Receptor Interaction in the Obese-Hyperglycemic Mouse
Kahn, C. R., Neville, D. M., & Roth, J. (1973) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)44468-2 · Cited by 410 · see citing works
Insulin Receptor: Evidence That It Is a Protein Kinase
Roth, R. A., & Cassell, D. J. (1983) · Science · doi:10.1126/science.6849137 · Cited by 409 · see citing works
Ebina, Y., Araki, E., Taira, M., Shimada, F., Mori, M., Craik, C. S., Siddle, K., Pierce, S. B., Roth, R. A., & Rutter, W. J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.3.704 · Cited by 390 · see citing works
Pilch, P. F., & Czech, M. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)86092-1 · Cited by 388 · see citing works
Larner, J., Galasko, G. T., Cheng, K., DePaoli-Roach, A. A., Huang, L., Daggy, P., & Kellogg, J. (1979) · Science · doi:10.1126/science.228395 · Cited by 370 · see citing works
Tyrosine-specific protein kinase activity is associated with the purified insulin receptor.
Kasuga, M., Fujita‐Yamaguchi, Y., Blithe, D., & Kahn, C. R. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.8.2137 · Cited by 318 · see citing works
Self-citationPurification of insulin receptor with full binding activity.
Fujita‐Yamaguchi, Y., Choi, S., Sakamoto, Y., & Itakura, K. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32535-3 · Cited by 273 · see citing works
Insulin receptor: covalent labeling and identification of subunits.
Jacobs, S., Hazum, E., Shechter, Y., & Cuatrecasas, P. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.10.4918 · Cited by 243 · see citing works
Kasuga, M., HEDO, J. A., Yamada, K. M., & Kahn, C. R. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34032-8 · Cited by 220 · see citing works
Self-citationHEDO, J. A., Kahn, C. R., Hayashi, M., Yamada, K. M., & Kasuga, M. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44600-x · Cited by 217 · see citing works
Self-citationKasuga, M., Kahn, C. R., HEDO, J. A., OBBERGHEN, E. V., & Yamada, K. M. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.6917 · Cited by 213 · see citing works
Self-citationOBBERGHEN, E. V., Rossi, B., Kowalski‐Chauvel, A., Gazzano, H., & Ponzio, G. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.4.945 · Cited by 212 · see citing works
Photoaffinity labeling of insulin receptor proteins of liver plasma membrane preparations
Yip, C. C., Yeung, C. W. T., & Moule, M. L. (1980) · Biochemistry · doi:10.1021/bi00542a011 · Cited by 196 · see citing works
Characterization of the insulin receptor kinase purified from human placental membranes.
Kasuga, M., Fujita‐Yamaguchi, Y., Blithe, D., White, M. F., & Kahn, C. R. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44373-0 · Cited by 195 · see citing works
Self-citationHuman Diabetes Associated with a Mutation in the Tyrosine Kinase Domain of the Insulin Receptor
Odawara, M., Kadowaki, T., Yamamoto, R., Shibasaki, Y., Tobe, K., Accili, D., Bevins, C. L., Mikami, Y., Matsuura, N., Akanuma, Y., et al. (1989) · Science · doi:10.1126/science.2544998 · Cited by 191 · see citing works
Self-citationBiosynthetic labeling of insulin receptor: studies of subunits in cultured human IM-9 lymphocytes.
OBBERGHEN, E. V., Ksauga, M., Cam, A. L., HEDO, J. A., Itin, A., & Harrison, L. C. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.2.1052 · Cited by 183 · see citing works
Seals, J. R., & Czech, M. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43595-8 · Cited by 175 · see citing works
HEDO, J. A., Kasuga, M., OBBERGHEN, E. V., Roth, J., & Kahn, C. R. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.8.4791 · Cited by 160 · see citing works
Self-citationEffects of epinephrine and insulin on phosphopeptide metabolism in adipocytes.
Avruch, J., Leone, G. R., & Martin, D. B. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33770-5 · Cited by 133 · see citing works
Insulin-stimulated protein phosphorylation in 3T3-L1 preadipocytes.
Smith, C. J., Wejksnora, P. J., Warner, J. R., Rubin, C. S., & Rosen, O. M. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.6.2725 · Cited by 132 · see citing works
Kiechle, F. L., Jarett, L., Kotagal, N., & Popp, D. A. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69706-1 · Cited by 100 · see citing works
Saltiel, A. R., Siegel, M. I., Jacobs, S., & Cuatrecasas, P. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.11.3513 · Cited by 85 · see citing works
Kasuga, M., OBBERGHEN, E. V., Yamada, K. M., & Harrison, L. C. (1981) · Diabetes · doi:10.2337/diab.30.4.354 · Cited by 64 · see citing works
Self-citationEffects of Fasting and Refeeding on Insulin Receptors and Glucose Metabolism in Rat Adipocytes
Kasuga, M., A, Y. A., YasuhikoIwamoto, & Kosaka, K. (1977) · Endocrinology · doi:10.1210/endo-100-5-1384 · Cited by 64 · see citing works
Self-citationYamamoto, R., Shiba, T., Tobe, K., Shibasaki, Y., Koshio, O., Izumi, T., Odawara, M., Mikami, Y., Matsuura, N., Akanuma, Y., et al. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-70-4-869 · Cited by 14 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments
Wang, M., Tan, Y., Shi, Y., Wang, X., Liao, Z., & Wei, P. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00568 · Cited by 231 · see citing works
Diabetic Cardiomyopathy: 2023 Update by the International Multidisciplinary Board of Experts
Арманович, А. А., Fogacci, F., Вачиковна, П. Н., Kakrurskiy, L., Коган, Е. А., Urazova, O. I., Kobalava, Z. D., Михалева, Л. М., Vandysheva, R. A., Zarina, G., et al. (2023) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2023.102052 · Cited by 52 · see citing works
Mir, R., Jeelani, M., Alharthi, M. H., Rizvi, S. F., Sohail, S. K., Wani, J. I., Sabah, Z. U., BinAfif, W. F., Nandi, P. S., Alshahrani, A. M., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062770 · Cited by 40 · see citing works
Liu, F., Zhu, B., An, Y., Zhou, Z., Xiong, P., Li, X., Yang, M., He, T., Chen, F., & Bu-ling, W. (2024) · International Journal of Oral Science · doi:10.1038/s41368-024-00313-z · Cited by 28 · see citing works
Li, Y., Jiang, J., Yang, J., Xiao, L., Hua, Q., & Zou, Y. (2021) · BMC Ophthalmology · doi:10.1186/s12886-021-01946-y · Cited by 26 · see citing works
Receptor tyrosine kinases as a therapeutic target by natural compounds in cancer treatment
Balogun, T. A., Ige, O. M., Alausa, A. O., Onyeani, C. O., Tiamiyu, Z. A., Omoboyowa, D. A., Saibu, O. A., & Abdullateef, O. T. (2021) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-021-00346-9 · Cited by 14 · see citing works
Zhang, S., Liu, Q., Yang, C., Li, X., Chen, Y., Wu, J., Fan, W., Liu, Y., & Lin, J. (2023) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2023.103727 · Cited by 9 · see citing works
Cimmino, I., Faggiano, A., Perruolo, G., Modica, R., Bottiglieri, F., Covelli, B., Colao, A., Bèguinot, F., Formisano, P., & Oriente, F. (2020) · Endocrine · doi:10.1007/s12020-020-02287-4 · Cited by 7 · see citing works
Zhang, Y., Lan, M., Liu, C., Wang, T., Liu, C., Wu, S., & Meng, Q. (2023) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2023.106420 · Cited by 5 · see citing works
ANTIDIABETIC PROPERTY OF MEDICINAL PLANTS IN MALAYSIA
Malaysia, U. P., Ishak, N. A., Hamid, M., Malaysia, U. P., Zabidi, N. A., & Malaysia, U. P. (2021) · Journal of Sustainability Science and Management · doi:10.46754/jssm.2021.12.022 · Cited by 4 · see citing works
Petunina, N. A., Валерьевна, Г. Е., Кузина, И. А., Недосугова, Л. В., Степановна, М. Н., & Эдуардовна, Т. М. (2022) · Diabetes Mellitus · doi:10.14341/dm12859 · Cited by 3 · see citing works
SX-fraction: Promise for novel treatment of type 2 diabetes
Konno, S. (2020) · World Journal of Diabetes · doi:10.4239/wjd.v11.i12.572 · Cited by 2 · see citing works
Fisiopatología y mecanismos de acción del ejercicio en el manejo de la diabetes mellitus tipo 2
León-Ariza, H. H., Guardela, M. J. R., & Barrera, A. F. C. (2023) · Revista Colombiana de Endocrinología Diabetes & Metabolismo · doi:10.53853/encr.10.2.790 · Cited by 2 · see citing works
Le récepteur de l’insuline a 50 ans – Revue des progrès accomplis
MEYTS, P. D. (2022) · Biologie Aujourd hui · doi:10.1051/jbio/2022007
“NO” controversy?: A controversial role in insulin signaling of diabetic encephalopathy
Chen, X., Song, Y., Hong, Y., Zhang, X. M., Li, Q., & Zhou, H. (2024) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2024.112346
- Authors
- KASUGA, M.
- Affiliations
- The Institute of Medical Science, Asahi Life Foundation (JP)
- Corresponding author
- KASUGA, Masato
- ORCID
- KASUGA, Masato
- Venue
- Proceedings of the Japan Academy, Series B
- Publisher
- Japan Academy
- Published
- 2019-12-11
- Volume
- 95
- Issue
- 10
- Pages
- 581-589
- ISSN
- 0386-2208 (ISSN-L)
- 1349-2896
- PMC
- PMC6920081
- OpenAlex
- W2995389313
- Cited by
- 15
- References
- 38
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 3
- FWCI
- 0.18
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Proceedings of the Japan Academy Series B (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- insulin receptor, insulin resistance, acanthosis nigricans, tyrosine kinase activity, receptor subunits, tyrosine phosphorylation, insulin signaling, receptor mutations, ATP binding site, insulin action
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Animals, Binding Sites, Humans, Insulin, Insulin Resistance, Mutation, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Receptor, Insulin, Tyrosine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
