somatomedin receptors


Summary: Cell surface receptors that bind somatomedins and trigger intracellular changes which influence the behavior of cells. Studies have disclosed two types of receptors for this family of peptide hormones. The type I receptor is homologous to the insulin receptor and has tyrosine kinase activity. The type II receptor is identical to the mannose-6-phosphate receptor which is important in trafficking of lysosomal enzymes.

Top Publications

  1. Pollak M, Schernhammer E, Hankinson S. Insulin-like growth factors and neoplasia. Nat Rev Cancer. 2004;4:505-18 pubmed
  2. Hubbard R, BaMaung N, Palazzo F, Zhang Q, Kovar P, Osterling D, et al. Pyrazolo[3,4-d]pyrimidines as potent inhibitors of the insulin-like growth factor receptor (IGF-IR). Bioorg Med Chem Lett. 2007;17:5406-9 pubmed
    ..The synthesis and subsequent optimization of this class of compounds led to the discovery of 14, a compound that possesses in vivo IGF-IR inhibitory activity. ..
  3. Ullrich A, Gray A, Tam A, Yang Feng T, Tsubokawa M, Collins C, et al. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986;5:2503-12 pubmed
  4. Gabillard J, Duval H, Cauty C, Rescan P, Weil C, Le Bail P. Differential expression of the two GH genes during embryonic development of rainbow trout Oncorhynchus mykiss in relation with the IGFs system. Mol Reprod Dev. 2003;64:32-40 pubmed publisher
    ..The relationship observed between the expression of different component of the GH/IGF system seems to indicate that this system could be functional early on during embryonic development...
  5. Wood A, Duan C, Bern H. Insulin-like growth factor signaling in fish. Int Rev Cytol. 2005;243:215-85 pubmed
    ..This review is intended as a summary of our understanding of IGF signaling, as revealed through research into the expression, function, and evolution of IGF ligands, receptors, and binding proteins in fish. ..
  6. Denley A, Cosgrove L, Booker G, Wallace J, Forbes B. Molecular interactions of the IGF system. Cytokine Growth Factor Rev. 2005;16:421-39 pubmed
    ..The complex molecular interactions of the ligands and receptors of the IGF system underlie all the biological actions mentioned above and will be the focus of this review. ..
  7. Schramm H. A unique intracellular, extracellular and transmembrane circulation of potassium ions in the auditory inner ear as an anticarcinogenic principle? Part 1. Inflamm Allergy Drug Targets. 2010;9:109-19 pubmed
  8. Drucker L, Uziel O, Tohami T, Shapiro H, Radnay J, Yarkoni S, et al. Thalidomide down-regulates transcript levels of GC-rich promoter genes in multiple myeloma. Mol Pharmacol. 2003;64:415-20 pubmed
    ..Indeed, this selectivity delineates GC-rich promoter genes as a unique group eligible for specific drug targeting. ..
  9. Bunn R, Fowlkes J. Insulin-like growth factor binding protein proteolysis. Trends Endocrinol Metab. 2003;14:176-81 pubmed

More Information


  1. Morgillo F, Woo J, Kim E, Hong W, Lee H. Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib. Cancer Res. 2006;66:10100-11 pubmed
  2. van der Vorm E, Kuipers A, Bonenkamp J, Kleijer W, Van Maldergem L, Herwig J, et al. Patients with lipodystrophic diabetes mellitus of the Seip-Berardinelli type, express normal insulin receptors. Diabetologia. 1993;36:172-4 pubmed
    ..These findings demonstrate that the primary genetic lesion in Seip-Berardinelli's lipodystrophy is outside the insulin receptor gene and that an involvement of the insulin-like growth factor I receptor is also unlikely. ..
  3. Hubbard R, BaMaung N, Fidanze S, Erickson S, Palazzo F, Wilsbacher J, et al. Development of multitargeted inhibitors of both the insulin-like growth factor receptor (IGF-IR) and members of the epidermal growth factor family of receptor tyrosine kinases. Bioorg Med Chem Lett. 2009;19:1718-21 pubmed publisher
    ..Herein, we disclose the structure activity relationships that led to the synthesis and biological characterization of 14, a novel small molecule inhibitor of both IGF-IR and members of the epidermal growth factor family of RTKs. ..
  4. Gu Y, Zhang K, Li M, Li X, Zhu L, Wang J, et al. [Developmental expression changes of insulin-like growth factors (IGFs) system genes in longissimus dorsi muscle of two pig breeds]. Yi Chuan. 2009;31:837-43 pubmed
  5. Tollefsen S, Lajara R, McCusker R, Clemmons D, Rotwein P. Insulin-like growth factors (IGF) in muscle development. Expression of IGF-I, the IGF-I receptor, and an IGF binding protein during myoblast differentiation. J Biol Chem. 1989;264:13810-7 pubmed
  6. Rosendahl A, Forsberg G. Influence of IGF-IR stimulation or blockade on proliferation of human renal cell carcinoma cell lines. Int J Oncol. 2004;25:1327-36 pubmed
    ..In light of this and with the functional data presented in this study, interference with this growth factor system may provide a novel therapeutic approach in renal cancer therapy. ..
  7. Acquafredda A, Murrieta D, Schimpff R, Donnadieu M, Job J. Insulin-like growth factor I receptors on human erythrocytes from normal children: relationship with age. Horm Metab Res. 1988;20:570-3 pubmed
  8. Weiland M, Bahr F, Hohne M, Schurmann A, Ziehm D, Joost H. The signaling potential of the receptors for insulin and insulin-like growth factor I (IGF-I) in 3T3-L1 adipocytes: comparison of glucose transport activity, induction of oncogene c-fos, glucose transporter mRNA, and DNA-synthesis. J Cell Physiol. 1991;149:428-35 pubmed
    ..These data indicate that in 3T3-L1 cells the alpha-subunits of insulin and IGF-I receptors have an equal potential to stimulate a metabolic and a mitogenic response. ..
  9. Telford N, Hogan A, Franz C, Schultz G. Expression of genes for insulin and insulin-like growth factors and receptors in early postimplantation mouse embryos and embryonal carcinoma cells. Mol Reprod Dev. 1990;27:81-92 pubmed
    ..g., maternal) sources of insulin. Both IGF-I and IGF-II could act as paracrine or autocrine growth factors, and IGF-II is the more abundant growth factor in differentiating F9 cells. ..
  10. Ivanov V, Zhou H, Ghandhi S, Karasic T, Yaghoubian B, Amundson S, et al. Radiation-induced bystander signaling pathways in human fibroblasts: a role for interleukin-33 in the signal transmission. Cell Signal. 2010;22:1076-87 pubmed publisher
  11. Figueroa J, De Raad S, Speights V, Rinehart J. Gene expression of insulin-like growth factors and receptors in neoplastic prostate tissues: correlation with clinico-pathological parameters. Cancer Invest. 2001;19:28-34 pubmed
    ..We conclude that differential expression of certain IGF system components may be important in the biology and clinical behavior of prostate cancer. ..
  12. Matthews K, Devlin G, Conaglen J, Stuart S, Mervyn Aitken W, Bass J. Changes in IGFs in cardiac tissue following myocardial infarction. J Endocrinol. 1999;163:433-45 pubmed
  13. Ahmad N, Keehn C, Coppola D. The expression of insulin-like growth factor-I receptor correlates with Fuhrman grading of renal cell carcinomas. Hum Pathol. 2004;35:1132-6 pubmed
    ..0001). Thus we report the novel finding of significant statistical correlation between IGF-IR protein expression and Fuhrman nuclear grade of RCC, and consequentially with patient survival. ..
  14. Dos Santos E, Dieudonne M, Leneveu M, Serazin V, Rincheval V, Mignotte B, et al. Effects of 17beta-estradiol on preadipocyte proliferation in human adipose tissue: Involvement of IGF1-R signaling. Horm Metab Res. 2010;42:514-20 pubmed publisher
    ..Taken together, these data reinforce the concept of cross-talk between IGF1- and ER-signaling pathways in preadipocytes and indicate that IGFI may be a critical regulator of estrogen-mediated preadipose growth. ..
  15. Burroughs K, Howe S, Okubo Y, Fuchs Young R, LeRoith D, Walker C. Dysregulation of IGF-I signaling in uterine leiomyoma. J Endocrinol. 2002;172:83-93 pubmed
    ..Autocrine stimulation of the IGF-IR may, therefore, play a role in regulating the normal growth of the myometrium, and dysregulation of IGF-I signaling could contribute to the neoplastic growth of uterine leiomyomas. ..
  16. Cruickshank J, Heald A, Anderson S, Cade J, Sampayo J, Riste L, et al. Epidemiology of the insulin-like growth factor system in three ethnic groups. Am J Epidemiol. 2001;154:504-13 pubmed
    ..IGF-II showed a strong ethnic difference but was unrelated to other variables. These data indicate considerable potential for exploring disease-IGF system relations in population samples. ..
  17. Tsao T, Fawcett J, Fervenza F, Hsu F, Huie P, Sibley R, et al. Expression of insulin-like growth factor-I and transforming growth factor-beta in hypokalemic nephropathy in the rat. Kidney Int. 2001;59:96-105 pubmed
    ..It is also conceivable that TGF-beta may be a cause of the tubulointerstitial infiltrate. Finally, the low circulating IGF-I levels likely contribute to the impaired body growth. ..
  18. Saito T, Fukui K, Akutsu S, Nakagawa Y, Ishibashi K, Nagata J, et al. Effects of diet consistency on the expression of insulin-like growth factors (IGFs), IGF receptors and IGF binding proteins during the development of rat masseter muscle soon after weaning. Arch Oral Biol. 2004;49:777-82 pubmed
    ..These findings suggest that the changes in expression of IGF-I, IGF-II, IGFR2, IGFBP3, IGFBP4 and IGFBP6 are associated with the fibre-type alteration of rat masseter muscle in response to diet consistency soon after weaning. ..
  19. Lorch J, Posner M, Wirth L, Haddad R. Seeking alternative biological therapies: the future of targeted molecular treatment. Oral Oncol. 2009;45:447-53 pubmed publisher
    ..This article summarizes the most important recent developments in the targeted treatment of SCCHN and provides an overview of pathways and promising potential targets that could impact the treatment of patients with SCCHN in the future. ..
  20. Phan T, See P, Tran E, Nguyen T, Chan S, Lee S, et al. Suppression of insulin-like growth factor signalling pathway and collagen expression in keloid-derived fibroblasts by quercetin: its therapeutic potential use in the treatment and/or prevention of keloids. Br J Dermatol. 2003;148:544-52 pubmed
  21. Goel H, Fornaro M, Moro L, Teider N, Rhim J, King M, et al. Selective modulation of type 1 insulin-like growth factor receptor signaling and functions by beta1 integrins. J Cell Biol. 2004;166:407-18 pubmed
    ..This study unravels a novel mechanism mediated by the integrin cytoplasmic domain that differentially regulates cell adhesion to LN and cell proliferation in response to IGF. ..
  22. Lee Y, Hintz R, James P, Lee P, Shively J, Powell D. Insulin-like growth factor (IGF) binding protein complementary deoxyribonucleic acid from human HEP G2 hepatoma cells: predicted protein sequence suggests an IGF binding domain different from those of the IGF-I and IGF-II receptors. Mol Endocrinol. 1988;2:404-11 pubmed
  23. Laureys G, Barton D, Ullrich A, Francke U. Chromosomal mapping of the gene for the type II insulin-like growth factor receptor/cation-independent mannose 6-phosphate receptor in man and mouse. Genomics. 1988;3:224-9 pubmed
    ..The CIM6PR/IGF2R locus in man is asyntenic with the genes encoding IGF-II (IGF2), the IGF-I receptor (IGF1R), and the cation-dependent mannose 6-phosphate receptor (CDM6PR). ..
  24. Baserga R, Sell C, Porcu P, Rubini M. The role of the IGF-I receptor in the growth and transformation of mammalian cells. Cell Prolif. 1994;27:63-71 pubmed
    ..The picture emerging from these studies is that several transforming agents may exert their growth promoting effects through the direct or indirect activation of the IGF autocrine loop. ..
  25. Morris B. A forkhead in the road to longevity: the molecular basis of lifespan becomes clearer. J Hypertens. 2005;23:1285-309 pubmed
    ..Current progress bodes well for an ever-increasing length of healthy life for those who adapt emerging knowledge personally (so-called 'longevitarians'). ..
  26. Knowlden J, Jones H, Barrow D, Gee J, Nicholson R, Hutcheson I. Insulin receptor substrate-1 involvement in epidermal growth factor receptor and insulin-like growth factor receptor signalling: implication for Gefitinib ('Iressa') response and resistance. Breast Cancer Res Treat. 2008;111:79-91 pubmed
    ..Treatment with gefitinib alters the dynamics of this system, promoting IGF-IR signalling, the dominant gefitinib-resistant growth regulatory pathway in Tam-R cells, thus, potentially limiting its efficacy. ..
  27. Forbes K, Westwood M. The IGF axis and placental function. a mini review. Horm Res. 2008;69:129-37 pubmed publisher
  28. Gee J, Robertson J, Gutteridge E, Ellis I, Pinder S, Rubini M, et al. Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer. Endocr Relat Cancer. 2005;12 Suppl 1:S99-S111 pubmed
    ..IGF-1R inhibitors may also prove valuable in ER- patients, since considerable IGF-1R signalling activity was apparent within approximately 50% of such tumours. ..
  29. Scavo L, Shuldiner A, Serrano J, Dashner R, Roth J, De Pablo F. Genes encoding receptors for insulin and insulin-like growth factor I are expressed in Xenopus oocytes and embryos. Proc Natl Acad Sci U S A. 1991;88:6214-8 pubmed
    ..The expression of receptors for insulin and IGF-I in early Xenopus embryos and their apparent distinct developmental regulation suggest that these molecules and their ligands may be important in early Xenopus development. ..
  30. Surmacz E, Nugent P, Pietrzkowski Z, Baserga R. The role of the IGF1 receptor in the regulation of cdc2 mRNA levels in fibroblasts. Exp Cell Res. 1992;199:275-8 pubmed
    ..The importance of the IGF-1/IGF-1 receptor interaction in regulating the levels of cdc2 mRNA was further confirmed by showing that an antisense oligodeoxynucleotide to the IGF-1 receptor RNA inhibited the IGF-1-mediated increase. ..
  31. Armstrong D, Baxter G, Hogg C, Woad K. Insulin-like growth factor (IGF) system in the oocyte and somatic cells of bovine preantral follicles. Reproduction. 2002;123:789-97 pubmed
    ..In conclusion, although the IGF ligands are not expressed in preantral follicles, mRNAs encoding the type 1 IGF receptor, and IGFBP-2 and -3 were present and showed unique spatial patterns of expression within preantral follicles. ..
  32. Brown A, Chiariotti L, Orlowski C, Mehlman T, Burgess W, Ackerman E, et al. Nucleotide sequence and expression of a cDNA clone encoding a fetal rat binding protein for insulin-like growth factors. J Biol Chem. 1989;264:5148-54 pubmed
    ..Thus, the rat IGF binding protein that we have cloned appears to be a distinct member of a family of related IGF binding proteins. We postulate that the structurally distinct IGF binding proteins may have different biological functions. ..
  33. Baron V, Calleja V, Ferrari P, Alengrin F, Van Obberghen E. p125Fak focal adhesion kinase is a substrate for the insulin and insulin-like growth factor-I tyrosine kinase receptors. J Biol Chem. 1998;273:7162-8 pubmed
  34. Vestergaard M, Purup S, Frystyk J, Løvendahl P, Sørensen M, Riis P, et al. Effects of growth hormone and feeding level on endocrine measurements, hormone receptors, muscle growth and performance of prepubertal heifers. J Anim Sci. 2003;81:2189-98 pubmed
    ..The results suggest that in skeletal muscle, the anabolic effects of exogenous GH are related to endocrine changes in the GH-IGF axis, whereas the effects of feeding level also seem to rely on IGF receptor density in the muscles. ..
  35. Pavelic K, Bukovic D, Pavelic J. The role of insulin-like growth factor 2 and its receptors in human tumors. Mol Med. 2002;8:771-80 pubmed
  36. Corvera S. Insulin stimulates the assembly of cytosolic clathrin onto adipocyte plasma membranes. J Biol Chem. 1990;265:2413-6 pubmed
    ..These results suggest that insulin induces an increase in the assembly of cytosolic clathrin onto the plasma membrane in conjunction with its ability to increase the concentration of receptors on the cell surface. ..
  37. Manes S, Kremer L, Albar J, Mark C, Llopis R, Martinez C. Functional epitope mapping of insulin-like growth factor I (IGF-I) by anti-IGF-I monoclonal antibodies. Endocrinology. 1997;138:905-15 pubmed
    ..Finally, IGF-I-promoted survival can be blocked with mAb specific for target epitopes, and their potential use in tumor cell growth control is discussed. ..
  38. Benito M, Valverde A, Lorenzo M. IGF-I: a mitogen also involved in differentiation processes in mammalian cells. Int J Biochem Cell Biol. 1996;28:499-510 pubmed
    ..However, IGF-I induces proliferation and differentiation in fetal brown adipocytes, suggesting that both cellular processes are not necessarily mutually exclusive in fetal cells. ..
  39. Shrader C, Bailey K, Konat G, Cilento E, Reilly F. Insulin enhances proliferation and viability of human umbilical vein endothelial cells. Arch Dermatol Res. 2009;301:159-66 pubmed publisher
    ..These data provide new insights into the beneficial effects of insulin on vascularization and tissue viability, providing a mechanistic link to the enhancement of healing in acutely stretched skin. ..
  40. Tamura K, Kobayashi M, Ishii Y, Tamura T, Hashimoto K, Nakamura S, et al. Primary structure of rat insulin-like growth factor-I and its biological activities. J Biol Chem. 1989;264:5616-21 pubmed
    ..Rat IGF-I showed 65% activity in the radioreceptor, 28.6% activity in the lipogenesis and 22.5% activity in the free fatty acid release inhibition assays as compared to human IGF-I on a protein quantity basis. ..
  41. McCabe K, Shiau C, Bronner Fraser M. Identification of candidate secreted factors involved in trigeminal placode induction. Dev Dyn. 2007;236:2925-35 pubmed
  42. Viereck V, Siggelkow H, Pannem R, Braulke T, Scharf J, Kubler B. Alteration of the insulin-like growth factor axis during in vitro differentiation of the human osteosarcoma cell line HOS 58. J Cell Biochem. 2007;102:28-40 pubmed
    ..These data are indicative for a role of the IGF axis during the in vitro differentiation of HOS 58 cells. ..
  43. Helle S, Lønning P. Insulin-like growth factors in breast cancer. Acta Oncol. 1996;35 Suppl 5:19-22 pubmed
  44. Playford M, Bicknell D, Bodmer W, Macaulay V. Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc Natl Acad Sci U S A. 2000;97:12103-8 pubmed
    ..In conclusion, we have shown that IGF-1 causes tyrosine phosphorylation and stabilization of beta-catenin. These effects may contribute to transformation, cell migration, and a propensity for metastasis in vivo. ..
  45. Wood W, Cachianes G, Henzel W, Winslow G, Spencer S, Hellmiss R, et al. Cloning and expression of the growth hormone-dependent insulin-like growth factor-binding protein. Mol Endocrinol. 1988;2:1176-85 pubmed
    ..This expressed protein is identical to plasma-derived BP-53 in its immunoreactivity, high affinity binding of IGF-I and IGF-II, and mobility on sodium dodecyl sulfate gel electrophoresis. ..
  46. Gagarina V, Gabay O, Dvir Ginzberg M, Lee E, Brady J, Quon M, et al. SirT1 enhances survival of human osteoarthritic chondrocytes by repressing protein tyrosine phosphatase 1B and activating the insulin-like growth factor receptor pathway. Arthritis Rheum. 2010;62:1383-92 pubmed publisher
    ..For the first time, it has been demonstrated that SirT1 is a mediator of human chondrocyte survival via down-regulation of PTP1B, a potent proapoptotic protein that is elevated in OA cartilage. ..
  47. Latham K, Doherty A, Scott C, Schultz R. Igf2r and Igf2 gene expression in androgenetic, gynogenetic, and parthenogenetic preimplantation mouse embryos: absence of regulation by genomic imprinting. Genes Dev. 1994;8:290-9 pubmed
    ..For these genes, this finding invalidates models of genomic imprinting that require them to be inactive from the time of fertilization. ..
  48. Werther G, Hintz R, Rosenfeld R. Up-regulation of IGF-I receptors on IM-9 cells by IGF-II peptides. Horm Metab Res. 1989;21:109-12 pubmed
    ..This phenomenon is not mimicked by the structurally-related peptides IGF-I or insulin; The up-regulation is due to enhanced high affinity binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  49. Liu G, Wei Y, Wang Z, Wu D, Zhou A. Effects of dietary supplementation with cysteamine on growth hormone receptor and insulin-like growth factor system in finishing pigs. J Agric Food Chem. 2008;56:5422-7 pubmed publisher
    ..Moreover, the results also imply the possible physiologic role of the GH-IGF axis in mediating the dietary CS supplementation-supported growth of finishing pigs. ..
  50. Nagatomo T, Muta K, Ohga S, Ochiai M, Ohshima K, Hara T. Insulin-like growth factor-II: a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors. Exp Hematol. 2008;36:401-11 pubmed publisher
    ..These results suggest that IGF-II is produced by erythroid progenitors themselves, and has a crucial role in fetal erythropoiesis by modulating apoptosis and maturation in an autocrine fashion. ..
  51. Gammeltoft S, Ballotti R, Nielsen F, Kowalski A, Van Obberghen E. Receptors for insulin-like growth factors in the central nervous system: structure and function. Horm Metab Res. 1988;20:436-42 pubmed
    ..Based on these findings we suggest that IGF receptors in brain undergo changes during fetal development and malignant transformation.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  52. Kalus W, Zweckstetter M, Renner C, Sanchez Y, Georgescu J, Grol M, et al. Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions. EMBO J. 1998;17:6558-72 pubmed
    ..Compared with the full-length IGFBP-5, the smaller N-terminal fragments were less efficient inhibitors of the IGF-I receptor binding of IGFs. ..
  53. Parker A, Cheville J, Lohse C, Cerhan J, Blute M. Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma. J Urol. 2003;170:420-4 pubmed
    ..Evidence from this investigation is consistent with laboratory data suggesting that IGF-IR expression is associated with CC-RCC survival and could potentially represent a molecular avenue for therapeutic intervention. ..