Growth and the Insulin-Like Growth Factor-1 Receptor (IGF1R)

  • Maria Belen Roldan Martin
  • Selma Feldman Witchel


The insulin-like growth factor-1 receptor (IGF-1R) is a membrane-bound tyrosine kinase receptor capable of auto-phosphorylation following ligand binding. While IGF-1 is the major ligand for this receptor, both IGF-2 and insulin can bind to the IGF-1R. Following ligand binding and IGF-1R auto-phosphorylation, the insulin receptor substrate (IRS) proteins are tyrosine phosphorylated by the IGF-1R. Following phosphorylation of the IRS proteins, one intracellular signaling cascade activates PI3K leading to increased PIP3 production. Another major intracellular signaling pathway involves the Shc proteins with subsequent activation of RAS, RAF, and the extracellular signal-regulated kinase (ERK) pathways. IGF-1R activates other members of the MAP kinase family. The IGF-1R has much structural homology with the insulin receptor leading to the presence of hybrid receptors in some cells. The IGF-1/IGF-1R system plays critical roles in prenatal and postnatal growth. One patient with a duplication of the IGF1R gene was reported as having large birth weight, coarse facial features, and dysmorphic features reminiscent of Beckwith–Wiedemann. Loss-of-function mutations in the IGF-1R gene have been associated with intrauterine growth retardation (IUGR). Clinical observations have demonstrated that IGF-1 concentrations increase during puberty. Dysregulation of the IGF-1/insulin/IGF-1R system may contribute to the pathophysiology of premature adrenarche (PA) and polycystic ovary syndrome (PCOS). Polymorphisms in the IGF-1R gene and its homologues have been associated with lifespan in humans and other organisms, respectively. Generation of transgenic mice has revealed the importance of IGF-1/IGF-1R signaling in multiple tissues including brain, bone, pancreatic β-cells, skin, and muscle. Elucidation of the role of IGF-1R in cell proliferation, survival, and apoptosis will be useful to develop novel therapies for cancer.


Congenital Adrenal Hyperplasia Adrenal Androgen Zona Reticularis Insulin Receptor Substrate Protein IGF1R Gene 



Extracellular signal-regulated kinase


Growth hormone


Insulin-like growth factor


IGF-1 receptor


IGF-2 receptor


IGF-binding protein


Insulin receptor


Janus kinase 2


Mitogen-activated protein kinase


Premature adrenarche






Premature pubarche


Phosphatase and tensin homologue


Small for gestational age


Sex hormone-binding globulin


Signal transducer and activator of transcription


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Maria Belen Roldan Martin
    • 1
  • Selma Feldman Witchel
    • 2
  1. 1.Division of Pediatric EndocrinologyGregorio Marañón Hospital, Complutense University of MadridMadridSpain
  2. 2.Division of Pediatric EndocrinologyChildren’s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of MedicinePittsburghUSA

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