Downstream targets of IGF-1R

Downstream targets of IGF-1R. The binding of IGF-I or IGF-II to IGF-1R results in autophosphorylation of tyrosine residues in the receptor. This leads to activation of the kinase domain and also provides the docking sites necessary for adaptor proteins to bind, thereby beginning a diverse cascade of intracellular signaling. Pathways that have been well described include Grb2, which then signals though Ras, Raf, and ultimately MAPK, leading to cell proliferation. Additionally, recruitment of PI3K results in cell survival by diminishing apoptotic signals. More recently, investigators have shown that the mTOR pathway is important in regulating protein translation, and that inhibition of mTOR results in a feedback loop, leading to an increase in Akt phosphorylation.Abbreviations: 4EBP, eukaryotic translation initiation factor 4E binding protein; Grb2, growth factor receptor-bound protein 2; IGF-1R, insulin-like growth factor receptor 1; IRS, insulin receptor substrate; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; PIP3, phosphatidylinositol 3,4,5-triphosphate; PI3K, phosphatidylinositol 3′ kinase; Rheb, Ras homolog enriched in brain; SAPK/JNK, stress-activated protein kinase/c-Jun NH2-terminal kinase; SGK, ribosomal S6 kinase; TSC, tuberous sclerosis complex.

Publication

The Role of IGF-1R in Pediatric Malignancies. () Su Young Kim, et al. Oncologist. ;14(1):83-91. Figure: F1. All organisms Homo sapiens Mus musculus Rattus norvegicus Canis lupus familiaris Drosophila melanogaster

Disease mentions