Find IGF1R Products Interaction Network for IGF1R IGF1R Details

Related Pathways Huntington's Disease Signaling Synaptic Long Term Depression IGF-1 Signaling View All Pathways

Synonyms: A330103N21RIK, CD221, D930020L01, hyft, IGF-IR, IGF1 RECEPTOR, IGF1R, Igf1r beta, Igf1r beta isoform, IGFIRC, Igfr, IGFR1, JTK13, LOC51049, MGC142170, MGC142172, MGC18216, NM1

IGF1R Signaling

Insulin (IN), insulin-like growth factor-1 (IGF-1) (Somatomedin C) and insulin-like growth factor-2 (IGF-2) (Somatomedin A) activate cell signaling pathways through tyrosine kinase holoreceptors (tetrameric α2β2-receptors) composed of two hemi-receptors (half-receptors, α,β-heterodimers) composed of linked alpha and beta proteins. Insulin, IGF-1 and IGF-2 bind to these holoreceptors with different specificities and affinities depending upon the combinations of specific half-receptors. Insulin receptors exist as two isoforms, IR-A and IR-B, derived from different mRNAs. IR-A is expressed predominantly in the central nervous system, hematopoietic cells, buffy coat leukocytes, Epstein-Barr virus-transformed lymphocytes, fetal tissues and various malignant cells. IR-B is expressed predominantly in adipose tissue, liver and muscle. Holo-receptors can be composed of combinations of two insulin half-receptors (IR), two IGF-1 half-receptors or as hybrids composed of IR and IGF-1 half-receptors. IGF-I hemi-receptors can hetero-dimerize with either the A or B isoform IR hemi-receptor leading to the formation of A-type and B-type insulin/IGF-I hybrid receptors. IR-A:IGF-IR and the IR-B:IGF-IR hybrids have different binding affinities for insulin, IGF-I and IGF-II. The IGF-1R hemi-receptor typically dominates the downstream response to ligand binding to insulin hybrid receptors.

IGF-1 binds to IGF-1 homo- or hybrid holo-receptors and induces auto-phosphorylations within the cytoplasmic domain of the receptor followed by the binding of various adapter molecules that contribute to the specificity of down-stream signaling. IGF-1 stimulates the growth and survival of cells primarily through the activation of the PI3K/PDK1/Akt(PKB)/mTOR and the (SOS), RasGTPase/Raf-1/Mek/Erk signaling pathways which are linked to the receptor via adaptor molecules such as members of the insulin receptor substrate (IRS) family (IRS-1, IRS-2, IRS-3, IRS-4) and or Src homology 2 domain containing transforming protein (SHC). The IRS adaptors link to an array of downstream adaptors, such as Grb-2, Nck, Crk-II and CrkL that activate or modulate signaling pathways. IGF-1 is reported to promote cell spreading and contact with extracellular matrix through RACK-1, an IGF-1 receptor-interaction protein that also interacts with integrins and activated protein kinase C.