Insulin-like growth factor 1 receptor
Details
- Name
- Insulin-like growth factor 1 receptor
- Synonyms
- 2.7.10.1
- IGF-I receptor
- Insulin-like growth factor I receptor
- Gene Name
- IGF1R
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0001710|Insulin-like growth factor 1 receptor MKSGSGGGSPTSLWGLLFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGYLH ILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIF EMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYIVGNKPPKECGD LCPGTMEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSTCGKRACTENNECCHPECLGSCS APDNDTACVACRHYYYAGVCVPACPPNTYRFEGWRCVDRDFCANILSAESSDSEGFVIHD GECMQECPSGFIRNGSQSMYCIPCEGPCPKVCEEEKKTKTIDSVTSAQMLQGCTIFKGNL LINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSF YVLDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTR NNGERASCESDVLHFTSTTTSKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDG QDACGSNSWNMVDVDLPPNKDVEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSE ILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPSLPNGNLSYYIVRWQRQPQDGYLYRH NYCSKDKIPIRKYADGTIDIEEVTENPKTEVCGGEKGPCCACPKTEAEKQAEKEEAEYRK VFENFLHNSIFVPRPERKRRDVMQVANTTMSSRSRNTTAADTYNITDPEELETEYPFFES RVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTW EPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGN YTARIQATSLSGNGSWTDPVFFYVQAKTGYENFIHLIIALPVAVLLIVGGLVIMLYVFHR KRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMSRELGQGSFGMVYEGVAKG VVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIME LMTRGDLKSYLRSLRPEMENNPVLAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARN CMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGV VLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFL EIISSIKEEMEPGFREVSFYYSEENKLPEPEELDLEPENMESVPLDPSASSSSLPLPDRH SGHKAENGPGPGVLVLRASFDERQPYAHMNGGRKNERALPLPQSSTC
- Number of residues
- 1367
- Molecular Weight
- 154791.73
- Theoretical pI
- 5.54
- GO Classification
- FunctionsATP binding / identical protein binding / insulin binding / insulin receptor binding / insulin receptor substrate binding / insulin-like growth factor binding / insulin-like growth factor I binding / insulin-like growth factor-activated receptor activity / phosphatidylinositol 3-kinase binding / protein tyrosine kinase activityProcessesaxonogenesis / brain development / epidermis development / establishment of cell polarity / exocrine pancreas development / immune response / inactivation of MAPKK activity / insulin receptor signaling pathway / insulin-like growth factor receptor signaling pathway / male sex determination / mammary gland development / negative regulation of apoptotic process / negative regulation of muscle cell apoptotic process / negative regulation of protein kinase B signaling / negative regulation of sequence-specific DNA binding transcription factor activity / peptidyl-tyrosine autophosphorylation / phosphatidylinositol 3-kinase signaling / phosphatidylinositol-mediated signaling / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of cytokinesis / positive regulation of DNA replication / positive regulation of MAPK cascade / positive regulation of mitotic nuclear division / positive regulation of protein kinase B signaling / positive regulation of steroid hormone biosynthetic process / prostate gland epithelium morphogenesis / protein autophosphorylation / protein heterooligomerization / protein tetramerization / regulation of JNK cascade / response to vitamin E / signal transductionComponentscaveola / integral component of plasma membrane / intracellular membrane-bounded organelle / membrane / neuron projection / plasma membrane / receptor complex
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
- Pfam Domain Function
- Transmembrane Regions
- 936-959
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0020490|Insulin-like growth factor 1 receptor (IGF1R) ATGAAGTCTGGCTCCGGAGGAGGGTCCCCGACCTCGCTGTGGGGGCTCCTGTTTCTCTCC GCCGCGCTCTCGCTCTGGCCGACGAGTGGAGAAATCTGCGGGCCAGGCATCGACATCCGC AACGACTATCAGCAGCTGAAGCGCCTGGAGAACTGCACGGTGATCGAGGGCTACCTCCAC ATCCTGCTCATCTCCAAGGCCGAGGACTACCGCAGCTACCGCTTCCCCAAGCTCACGGTC ATTACCGAGTACTTGCTGCTGTTCCGAGTGGCTGGCCTCGAGAGCCTCGGAGACCTCTTC CCCAACCTCACGGTCATCCGCGGCTGGAAACTCTTCTACAACTACGCCCTGGTCATCTTC GAGATGACCAATCTCAAGGATATTGGGCTTTACAACCTGAGGAACATTACTCGGGGGGCC ATCAGGATTGAGAAAAATGCTGACCTCTGTTACCTCTCCACTGTGGACTGGTCCCTGATC CTGGATGCGGTGTCCAATAACTACATTGTGGGGAATAAGCCCCCAAAGGAATGTGGGGAC CTGTGTCCAGGGACCATGGAGGAGAAGCCGATGTGTGAGAAGACCACCATCAACAATGAG TACAACTACCGCTGCTGGACCACAAACCGCTGCCAGAAAATGTGCCCAAGCACGTGTGGG AAGCGGGCGTGCACCGAGAACAATGAGTGCTGCCACCCCGAGTGCCTGGGCAGCTGCAGC GCGCCTGACAACGACACGGCCTGTGTAGCTTGCCGCCACTACTACTATGCCGGTGTCTGT GTGCCTGCCTGCCCGCCCAACACCTACAGGTTTGAGGGCTGGCGCTGTGTGGACCGTGAC TTCTGCGCCAACATCCTCAGCGCCGAGAGCAGCGACTCCGAGGGGTTTGTGATCCACGAC GGCGAGTGCATGCAGGAGTGCCCCTCGGGCTTCATCCGCAACGGCAGCCAGAGCATGTAC TGCATCCCTTGTGAAGGTCCTTGCCCGAAGGTCTGTGAGGAAGAAAAGAAAACAAAGACC ATTGATTCTGTTACTTCTGCTCAGATGCTCCAAGGATGCACCATCTTCAAGGGCAATTTG CTCATTAACATCCGACGGGGGAATAACATTGCTTCAGAGCTGGAGAACTTCATGGGGCTC ATCGAGGTGGTGACGGGCTACGTGAAGATCCGCCATTCTCATGCCTTGGTCTCCTTGTCC TTCCTAAAAAACCTTCGCCTCATCCTAGGAGAGGAGCAGCTAGAAGGGAATTACTCCTTC TACGTCCTCGACAACCAGAACTTGCAGCAACTGTGGGACTGGGACCACCGCAACCTGACC ATCAAAGCAGGGAAAATGTACTTTGCTTTCAATCCCAAATTATGTGTTTCCGAAATTTAC CGCATGGAGGAAGTGACGGGGACTAAAGGGCGCCAAAGCAAAGGGGACATAAACACCAGG AACAACGGGGAGAGAGCCTCCTGTGAAAGTGACGTCCTGCATTTCACCTCCACCACCACG TCGAAGAATCGCATCATCATAACCTGGCACCGGTACCGGCCCCCTGACTACAGGGATCTC ATCAGCTTCACCGTTTACTACAAGGAAGCACCCTTTAAGAATGTCACAGAGTATGATGGG CAGGATGCCTGCGGCTCCAACAGCTGGAACATGGTGGACGTGGACCTCCCGCCCAACAAG GACGTGGAGCCCGGCATCTTACTACATGGGCTGAAGCCCTGGACTCAGTACGCCGTTTAC GTCAAGGCTGTGACCCTCACCATGGTGGAGAACGACCATATCCGTGGGGCCAAGAGTGAG ATCTTGTACATTCGCACCAATGCTTCAGTTCCTTCCATTCCCTTGGACGTTCTTTCAGCA TCGAACTCCTCTTCTCAGTTAATCGTGAAGTGGAACCCTCCCTCTCTGCCCAACGGCAAC CTGAGTTACTACATTGTGCGCTGGCAGCGGCAGCCTCAGGACGGCTACCTTTACCGGCAC AATTACTGCTCCAAAGACAAAATCCCCATCAGGAAGTATGCCGACGGCACCATCGACATT GAGGAGGTCACAGAGAACCCCAAGACTGAGGTGTGTGGTGGGGAGAAAGGGCCTTGCTGC GCCTGCCCCAAAACTGAAGCCGAGAAGCAGGCCGAGAAGGAGGAGGCTGAATACCGCAAA GTCTTTGAGAATTTCCTGCACAACTCCATCTTCGTGCCCAGACCTGAAAGGAAGCGGAGA GATGTCATGCAAGTGGCCAACACCACCATGTCCAGCCGAAGCAGGAACACCACGGCCGCA GACACCTACAACATCACCGACCCGGAAGAGCTGGAGACAGAGTACCCTTTCTTTGAGAGC AGAGTGGATAACAAGGAGAGAACTGTCATTTCTAACCTTCGGCCTTTCACATTGTACCGC ATCGATATCCACAGCTGCAACCACGAGGCTGAGAAGCTGGGCTGCAGCGCCTCCAACTTC GTCTTTGCAAGGACTATGCCCGCAGAAGGAGCAGATGACATTCCTGGGCCAGTGACCTGG GAGCCAAGGCCTGAAAACTCCATCTTTTTAAAGTGGCCGGAACCTGAGAATCCCAATGGA TTGATTCTAATGTATGAAATAAAATACGGATCACAAGTTGAGGATCAGCGAGAATGTGTG TCCAGACAGGAATACAGGAAGTATGGAGGGGCCAAGCTAAACCGGCTAAACCCGGGGAAC TACACAGCCCGGATTCAGGCCACATCTCTCTCTGGGAATGGGTCGTGGACAGATCCTGTG TTCTTCTATGTCCAGGCCAAAACAGGATATGAAAACTTCATCCATCTGATCATCGCTCTG CCCGTCGCTGTCCTGTTGATCGTGGGAGGGTTGGTGATTATGCTGTACGTCTTCCATAGA AAGAGAAATAACAGCAGGCTGGGGAATGGAGTGCTGTATGCCTCTGTGAACCCGGAGTAC TTCAGCGCTGCTGATGTGTACGTTCCTGATGAGTGGGAGGTGGCTCGGGAGAAGATCACC ATGAGCCGGGAACTTGGGCAGGGGTCGTTTGGGATGGTCTATGAAGGAGTTGCCAAGGGT GTGGTGAAAGATGAACCTGAAACCAGAGTGGCCATTAAAACAGTGAACGAGGCCGCAAGC ATGCGTGAGAGGATTGAGTTTCTCAACGAAGCTTCTGTGATGAAGGAGTTCAATTGTCAC CATGTGGTGCGATTGCTGGGTGTGGTGTCCCAAGGCCAGCCAACACTGGTCATCATGGAA CTGATGACACGGGGCGATCTCAAAAGTTATCTCCGGTCTCTGAGGCCAGAAATGGAGAAT AATCCAGTCCTAGCACCTCCAAGCCTGAGCAAGATGATTCAGATGGCCGGAGAGATTGCA GACGGCATGGCATACCTCAACGCCAATAAGTTCGTCCACAGAGACCTTGCTGCCCGGAAT TGCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATTTTGGTATGACGCGAGATATC TATGAGACAGACTATTACCGGAAAGGAGGGAAAGGGCTGCTGCCCGTGCGCTGGATGTCT CCTGAGTCCCTCAAGGATGGAGTCTTCACCACTTACTCGGACGTCTGGTCCTTCGGGGTC GTCCTCTGGGAGATCGCCACACTGGCCGAGCAGCCCTACCAGGGCTTGTCCAACGAGCAA GTCCTTCGCTTCGTCATGGAGGGCGGCCTTCTGGACAAGCCAGACAACTGTCCTGACATG CTGTTTGAACTGATGCGCATGTGCTGGCAGTATAACCCCAAGATGAGGCCTTCCTTCCTG GAGATCATCAGCAGCATCAAAGAGGAGATGGAGCCTGGCTTCCGGGAGGTCTCCTTCTAC TACAGCGAGGAGAACAAGCTGCCCGAGCCGGAGGAGCTGGACCTGGAGCCAGAGAACATG GAGAGCGTCCCCCTGGACCCCTCGGCCTCCTCGTCCTCCCTGCCACTGCCCGACAGACAC TCAGGACACAAGGCCGAGAACGGCCCCGGCCCTGGGGTGCTGGTCCTCCGCGCCAGCTTC GACGAGAGACAGCCTTACGCCCACATGAACGGGGGCCGCAAGAACGAGCGGGCCTTGCCG CTGCCCCAGTCTTCGACCTGCTGA
- Chromosome Location
- 15
- Locus
- 15q26.3
- External Identifiers
Resource Link UniProtKB ID P08069 UniProtKB Entry Name IGF1R_HUMAN GenBank Protein ID 804990 GenBank Gene ID X04434 GenAtlas ID IGF1R HGNC ID HGNC:5465 - General References
- Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E, et al.: Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986 Oct;5(10):2503-12. [Article]
- Abbott AM, Bueno R, Pedrini MT, Murray JM, Smith RJ: Insulin-like growth factor I receptor gene structure. J Biol Chem. 1992 May 25;267(15):10759-63. [Article]
- Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Cooke DW, Bankert LA, Roberts CT Jr, LeRoith D, Casella SJ: Analysis of the human type I insulin-like growth factor receptor promoter region. Biochem Biophys Res Commun. 1991 Jun 28;177(3):1113-20. [Article]
- Kasuya J, Paz IB, Maddux BA, Goldfine ID, Hefta SA, Fujita-Yamaguchi Y: Characterization of human placental insulin-like growth factor-I/insulin hybrid receptors by protein microsequencing and purification. Biochemistry. 1993 Dec 14;32(49):13531-6. [Article]
- Lee ST, Strunk KM, Spritz RA: A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes. Oncogene. 1993 Dec;8(12):3403-10. [Article]
- Tollefsen SE, Stoszek RM, Thompson K: Interaction of the alpha beta dimers of the insulin-like growth factor I receptor is required for receptor autophosphorylation. Biochemistry. 1991 Jan 8;30(1):48-54. [Article]
- Soos MA, Field CE, Siddle K: Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity. Biochem J. 1993 Mar 1;290 ( Pt 2):419-26. [Article]
- Kato H, Faria TN, Stannard B, Roberts CT Jr, LeRoith D: Role of tyrosine kinase activity in signal transduction by the insulin-like growth factor-I (IGF-I) receptor. Characterization of kinase-deficient IGF-I receptors and the action of an IGF-I-mimetic antibody (alpha IR-3). J Biol Chem. 1993 Feb 5;268(4):2655-61. [Article]
- Craparo A, O'Neill TJ, Gustafson TA: Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J Biol Chem. 1995 Jun 30;270(26):15639-43. [Article]
- Bailyes EM, Nave BT, Soos MA, Orr SR, Hayward AC, Siddle K: Insulin receptor/IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting. Biochem J. 1997 Oct 1;327 ( Pt 1):209-15. [Article]
- Furlanetto RW, Dey BR, Lopaczynski W, Nissley SP: 14-3-3 proteins interact with the insulin-like growth factor receptor but not the insulin receptor. Biochem J. 1997 Nov 1;327 ( Pt 3):765-71. [Article]
- Federici M, Porzio O, Zucaro L, Fusco A, Borboni P, Lauro D, Sesti G: Distribution of insulin/insulin-like growth factor-I hybrid receptors in human tissues. Mol Cell Endocrinol. 1997 May 16;129(2):121-6. [Article]
- Dey BR, Spence SL, Nissley P, Furlanetto RW: Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor. J Biol Chem. 1998 Sep 11;273(37):24095-101. [Article]
- Lin FT, Daaka Y, Lefkowitz RJ: beta-arrestins regulate mitogenic signaling and clathrin-mediated endocytosis of the insulin-like growth factor I receptor. J Biol Chem. 1998 Nov 27;273(48):31640-3. [Article]
- Baserga R: The IGF-I receptor in cancer research. Exp Cell Res. 1999 Nov 25;253(1):1-6. [Article]
- Wang J, Dai H, Yousaf N, Moussaif M, Deng Y, Boufelliga A, Swamy OR, Leone ME, Riedel H: Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Mol Cell Biol. 1999 Sep;19(9):6217-28. [Article]
- Dey BR, Furlanetto RW, Nissley P: Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. Biochem Biophys Res Commun. 2000 Nov 11;278(1):38-43. [Article]
- Lopaczynski W, Terry C, Nissley P: Autophosphorylation of the insulin-like growth factor I receptor cytoplasmic domain. Biochem Biophys Res Commun. 2000 Dec 29;279(3):955-60. [Article]
- Zong CS, Chan J, Levy DE, Horvath C, Sadowski HB, Wang LH: Mechanism of STAT3 activation by insulin-like growth factor I receptor. J Biol Chem. 2000 May 19;275(20):15099-105. [Article]
- Hellawell GO, Turner GD, Davies DR, Poulsom R, Brewster SF, Macaulay VM: Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease. Cancer Res. 2002 May 15;62(10):2942-50. [Article]
- Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A: Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002 Oct 18;277(42):39684-95. Epub 2002 Jul 22. [Article]
- Hermanto U, Zong CS, Li W, Wang LH: RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol. 2002 Apr;22(7):2345-65. [Article]
- Galvan V, Logvinova A, Sperandio S, Ichijo H, Bredesen DE: Type 1 insulin-like growth factor receptor (IGF-IR) signaling inhibits apoptosis signal-regulating kinase 1 (ASK1). J Biol Chem. 2003 Apr 11;278(15):13325-32. Epub 2003 Jan 28. [Article]
- Girnita L, Girnita A, Larsson O: Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8247-52. Epub 2003 Jun 23. [Article]
- Girnita A, Girnita L, del Prete F, Bartolazzi A, Larsson O, Axelson M: Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth. Cancer Res. 2004 Jan 1;64(1):236-42. [Article]
- Girnita L, Shenoy SK, Sehat B, Vasilcanu R, Girnita A, Lefkowitz RJ, Larsson O: {beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase. J Biol Chem. 2005 Jul 1;280(26):24412-9. Epub 2005 May 3. [Article]
- Yadav A, Kalita A, Dhillon S, Banerjee K: JAK/STAT3 pathway is involved in survival of neurons in response to insulin-like growth factor and negatively regulated by suppressor of cytokine signaling-3. J Biol Chem. 2005 Sep 9;280(36):31830-40. Epub 2005 Jul 5. [Article]
- Slaaby R, Schaffer L, Lautrup-Larsen I, Andersen AS, Shaw AC, Mathiasen IS, Brandt J: Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant. J Biol Chem. 2006 Sep 8;281(36):25869-74. Epub 2006 Jul 10. [Article]
- McElroy B, Powell JC, McCarthy JV: The insulin-like growth factor 1 (IGF-1) receptor is a substrate for gamma-secretase-mediated intramembrane proteolysis. Biochem Biophys Res Commun. 2007 Jul 13;358(4):1136-41. Epub 2007 May 21. [Article]
- Hartog H, Wesseling J, Boezen HM, van der Graaf WT: The insulin-like growth factor 1 receptor in cancer: old focus, new future. Eur J Cancer. 2007 Sep;43(13):1895-904. Epub 2007 Jul 10. [Article]
- Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
- Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
- Del Rincon SV, Rogers J, Widschwendter M, Sun D, Sieburg HB, Spruck C: Development and validation of a method for profiling post-translational modification activities using protein microarrays. PLoS One. 2010 Jun 28;5(6):e11332. doi: 10.1371/journal.pone.0011332. [Article]
- Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
- Mao Y, Shang Y, Pham VC, Ernst JA, Lill JR, Scales SJ, Zha J: Polyubiquitination of insulin-like growth factor I receptor (IGF-IR) activation loop promotes antibody-induced receptor internalization and down-regulation. J Biol Chem. 2011 Dec 2;286(48):41852-61. doi: 10.1074/jbc.M111.288514. Epub 2011 Oct 12. [Article]
- Garrett TP, McKern NM, Lou M, Frenkel MJ, Bentley JD, Lovrecz GO, Elleman TC, Cosgrove LJ, Ward CW: Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor. Nature. 1998 Jul 23;394(6691):395-9. [Article]
- Favelyukis S, Till JH, Hubbard SR, Miller WT: Structure and autoregulation of the insulin-like growth factor 1 receptor kinase. Nat Struct Biol. 2001 Dec;8(12):1058-63. [Article]
- Pautsch A, Zoephel A, Ahorn H, Spevak W, Hauptmann R, Nar H: Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation. Structure. 2001 Oct;9(10):955-65. [Article]
- Munshi S, Kornienko M, Hall DL, Reid JC, Waxman L, Stirdivant SM, Darke PL, Kuo LC: Crystal structure of the Apo, unactivated insulin-like growth factor-1 receptor kinase. Implication for inhibitor specificity. J Biol Chem. 2002 Oct 11;277(41):38797-802. Epub 2002 Jul 22. [Article]
- Munshi S, Hall DL, Kornienko M, Darke PL, Kuo LC: Structure of apo, unactivated insulin-like growth factor-1 receptor kinase at 1.5 A resolution. Acta Crystallogr D Biol Crystallogr. 2003 Oct;59(Pt 10):1725-30. Epub 2003 Sep 19. [Article]
- Velaparthi U, Wittman M, Liu P, Stoffan K, Zimmermann K, Sang X, Carboni J, Li A, Attar R, Gottardis M, Greer A, Chang CY, Jacobsen BL, Sack JS, Sun Y, Langley DR, Balasubramanian B, Vyas D: Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R). Bioorg Med Chem Lett. 2007 Apr 15;17(8):2317-21. Epub 2007 Feb 4. [Article]
- Mayer SC, Banker AL, Boschelli F, Di L, Johnson M, Kenny CH, Krishnamurthy G, Kutterer K, Moy F, Petusky S, Ravi M, Tkach D, Tsou HR, Xu W: Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment. Bioorg Med Chem Lett. 2008 Jun 15;18(12):3641-5. doi: 10.1016/j.bmcl.2008.04.044. Epub 2008 Apr 25. [Article]
- Wu J, Li W, Craddock BP, Foreman KW, Mulvihill MJ, Ji QS, Miller WT, Hubbard SR: Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor. EMBO J. 2008 Jul 23;27(14):1985-94. doi: 10.1038/emboj.2008.116. Epub 2008 Jun 19. [Article]
- Miller LM, Mayer SC, Berger DM, Boschelli DH, Boschelli F, Di L, Du X, Dutia M, Floyd MB, Johnson M, Kenny CH, Krishnamurthy G, Moy F, Petusky S, Tkach D, Torres N, Wu B, Xu W: Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment. Bioorg Med Chem Lett. 2009 Jan 1;19(1):62-6. doi: 10.1016/j.bmcl.2008.11.037. Epub 2008 Nov 17. [Article]
- Wittman MD, Carboni JM, Yang Z, Lee FY, Antman M, Attar R, Balimane P, Chang C, Chen C, Discenza L, Frennesson D, Gottardis MM, Greer A, Hurlburt W, Johnson W, Langley DR, Li A, Li J, Liu P, Mastalerz H, Mathur A, Menard K, Patel K, Sack J, Sang X, Saulnier M, Smith D, Stefanski K, Trainor G, Velaparthi U, Zhang G, Zimmermann K, Vyas DM: Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development. J Med Chem. 2009 Dec 10;52(23):7360-3. doi: 10.1021/jm900786r. [Article]
- Sampognaro AJ, Wittman MD, Carboni JM, Chang C, Greer AF, Hurlburt WW, Sack JS, Vyas DM: Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5027-30. doi: 10.1016/j.bmcl.2010.07.045. Epub 2010 Jul 15. [Article]
- Nemecek C, Metz WA, Wentzler S, Ding FX, Venot C, Souaille C, Dagallier A, Maignan S, Guilloteau JP, Bernard F, Henry A, Grapinet S, Lesuisse D: Design of potent IGF1-R inhibitors related to bis-azaindoles. Chem Biol Drug Des. 2010 Aug;76(2):100-6. doi: 10.1111/j.1747-0285.2010.00991.x. Epub 2010 Jun 9. [Article]
- Lesuisse D, Mauger J, Nemecek C, Maignan S, Boiziau J, Harlow G, Hittinger A, Ruf S, Strobel H, Nair A, Ritter K, Malleron JL, Dagallier A, El-Ahmad Y, Guilloteau JP, Guizani H, Bouchard H, Venot C: Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: advantages in comparison with competitive inhibitors. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2224-8. doi: 10.1016/j.bmcl.2011.03.003. Epub 2011 Mar 4. [Article]
- Buchanan JL, Newcomb JR, Carney DP, Chaffee SC, Chai L, Cupples R, Epstein LF, Gallant P, Gu Y, Harmange JC, Hodge K, Houk BE, Huang X, Jona J, Joseph S, Jun HT, Kumar R, Li C, Lu J, Menges T, Morrison MJ, Novak PM, van der Plas S, Radinsky R, Rose PE, Sawant S, Sun JR, Surapaneni S, Turci SM, Xu K, Yanez E, Zhao H, Zhu X: Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2394-9. doi: 10.1016/j.bmcl.2011.02.075. Epub 2011 Feb 23. [Article]
- Abuzzahab MJ, Schneider A, Goddard A, Grigorescu F, Lautier C, Keller E, Kiess W, Klammt J, Kratzsch J, Osgood D, Pfaffle R, Raile K, Seidel B, Smith RJ, Chernausek SD: IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation. N Engl J Med. 2003 Dec 4;349(23):2211-22. [Article]
- Kawashima Y, Kanzaki S, Yang F, Kinoshita T, Hanaki K, Nagaishi J, Ohtsuka Y, Hisatome I, Ninomoya H, Nanba E, Fukushima T, Takahashi S: Mutation at cleavage site of insulin-like growth factor receptor in a short-stature child born with intrauterine growth retardation. J Clin Endocrinol Metab. 2005 Aug;90(8):4679-87. Epub 2005 May 31. [Article]
- Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB01277 Mecasermin approved, investigational yes agonist Details DB04395 Phosphoaminophosphonic Acid-Adenylate Ester experimental unknown Details DB00030 Insulin human approved, investigational unknown activator Details DB00071 Insulin pork approved unknown Details DB05023 ATL1101 investigational unknown Details DB05184 XL228 investigational unknown Details DB12250 Cixutumumab investigational unknown Details DB05897 rhIGFBP-3 investigational unknown Details DB06075 Linsitinib investigational unknown inhibitor Details DB06343 Teprotumumab approved, investigational unknown binderantibody Details DB07156 (4Z)-6-bromo-4-({[4-(pyrrolidin-1-ylmethyl)phenyl]amino}methylidene)isoquinoline-1,3(2H,4H)-dione experimental unknown Details DB07474 3-[5-(1H-IMIDAZOL-1-YL)-7-METHYL-1H-BENZIMIDAZOL-2-YL]-4-[(PYRIDIN-2-YLMETHYL)AMINO]PYRIDIN-2(1H)-ONE experimental unknown Details DB12267 Brigatinib approved, investigational unknown inhibitor Details DB09098 Somatrem approved, investigational, withdrawn yes Details DB00046 Insulin lispro approved unknown activator Details DB01307 Insulin detemir approved unknown activator Details DB00047 Insulin glargine approved unknown activator Details DB01306 Insulin aspart approved unknown activator Details DB01309 Insulin glulisine approved unknown activator Details DB09564 Insulin degludec approved unknown activator Details DB14751 Mecasermin rinfabate approved yes agonist Details DB16637 KW-2450 free base experimental unknown inhibitor Details DB15399 BMS-754807 investigational unknown inhibitor Details DB11567 Insulin peglispro investigational unknown activator Details DB11564 Insulin argine experimental unknown activator Details DB09456 Insulin beef approved unknown activator Details DB11568 Insulin tregopil investigational unknown activator Details DB08804 Nandrolone decanoate approved, illicit unknown inducer Details DB11840 Dalotuzumab investigational yes antibodyregulator Details