Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Insulin-Like Growth Factor Receptor Type I (IGF1R) Signaling and Inflammation

  • Alexander AnnenkovEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_326


Historical Background

The IGF1R, a Protein Tyrosine Kinase Receptor, is expressed in many tissues and can be activated by its physiological ligands IGF-I and IGF-II, which are available systemically and from local sources. Activation of the IGF1R promotes cell growth and survival in a cell-autonomous manner. Because of a wide distribution of IGF1R and good bioavailability of its ligands, under pathological conditions this cytoprotective intracellular signaling pathway may be activated in cells that also receive stimulation by pathology-specific factors. Cross-regulation between IGF1R signaling and pathways activated by inflammation has recently been in the focus of attention in several laboratories because pro-inflammatory factors are a common cause of cellular pathology in many different conditions (O’Connor et al. 2008).

Resident parenchymal cells activated by pro-inflammatory cytokines in tissues affected by inflammation...

This is a preview of subscription content, log in to check access.


  1. Adams TE, Epa VC, Garrett TP, Ward CW. Structure and function of the type 1 insulin-like growth factor receptor. Cell Mol Life Sci. 2000;57(7):1050–93.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Brummer T, Schmitz-Peiffer C, Daly RJ. Docking proteins. FEBS J. 2010;277(21):4356–69.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2012;75(1):50–83.CrossRefGoogle Scholar
  4. Darling DL, Yingling J, Wynshaw-Boris A. Role of 14-3-3 proteins in eukaryotic signaling and development. Curr Top Dev Biol. 2005;68:281–315.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol. 2005;37(10):1974–84.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Hedrick SM. The cunning little vixen: Foxo and the cycle of life and death. Nat Immunol. 2009;10(10):1057–63.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140(6):900–17.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Kuemmerle JF. IGF-I elicits growth of human intestinal smooth muscle cells by activation of PI3K, PDK-1, and p70S6 kinase. Am J Physiol Gastrointest Liver Physiol. 2003;284(3):G411–22.CrossRefPubMedGoogle Scholar
  9. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007;129(7):1261–74.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Meng D, Lv DD, Fang J. Insulin-like growth factor-I induces reactive oxygen species production and cell migration through Nox4 and Rac1 in vascular smooth muscle cells. Cardiovasc Res. 2008;80(2):299–308.CrossRefPubMedGoogle Scholar
  11. Novosyadlyy R, Kurshan N, Lann D, Vijayakumar A, Yakar S, LeRoith D. Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum. Cell Death Differ. 2008;15(8):1304–17.CrossRefPubMedGoogle Scholar
  12. O’Connor JC, McCusker RH, Strle K, Johnson RW, Dantzer R, Kelley KW. Regulation of IGF-I function by proinflammatory cytokines: at the interface of immunology and endocrinology. Cell Immunol. 2008;252(1–2):91–110.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Pfaffenbach KT, Lee AS. The critical role of GRP78 in physiologic and pathologic stress. Curr Opin Cell Biol. 2012;23(2):150–6.CrossRefGoogle Scholar
  14. Takeda K, Noguchi T, Naguro I, Ichijo H. Apoptosis signal-regulating kinase 1 in stress and immune response. Annu Rev Pharmacol Toxicol. 2008;48:199–225.CrossRefPubMedGoogle Scholar
  15. Vardatsikos G, Sahu A, Srivastava AK. The insulin-like growth factor family: molecular mechanisms, redox regulation, and clinical implications. Antioxid Redox Signal. 2009;11(5):1165–90.CrossRefPubMedGoogle Scholar
  16. Wajant H, Scheurich P. TNFR1-induced activation of the classical NF-kappaB pathway. FEBS J. 2012;278(6):862–76.CrossRefGoogle Scholar
  17. Wu M, Yang X, Chan C. A dynamic analysis of IRS-PKR signaling in liver cells: a discrete modeling approach. PLoS One. 2009;4(12):e8040.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Xie D, Gore C, Zhou J, Pong RC, Zhang H, Yu L, et al. DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis. Proc Natl Acad Sci USA. 2009;106(47):19878–83.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Ye P, Kollias G, D’Ercole AJ. Insulin-like growth factor-I ameliorates demyelination induced by tumor necrosis factor-alpha in transgenic mice. J Neurosci Res. 2007;85(4):712–22.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008;454(7203):455–62.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Bone and Joint Research Unit, William Harvey Research InstituteQueen Mary University of LondonLondonUK