IGF1R

GeneName

IGF1R

Summary

IGF1R, also known as the insulin-like growth factor 1 receptor, is a 155 kDa transmembrane receptor that plays a crucial role in mediating the effects of insulin-like growth factor 1 (IGF-1). It is predominantly expressed in various tissues, including muscle, liver, and brain, and is localised to the plasma membrane as well as intracellular organelles such as the nucleolus and axon. IGF1R is involved in several biological pathways, including insulin receptor signalling and IGF receptor signalling pathways, and participates in processes such as cell migration, proliferation, and apoptosis regulation. The receptor functions through a complex of protein interactions, including binding to insulin and IGF-1, and its activity is regulated by various signalling cascades, including the phosphatidylinositol 3-kinase pathway.

Importance

IGF1R is relevant to: - Cancer biology due to its role in promoting cell proliferation and survival, making it a target for therapeutic interventions. - Metabolic disorders, as it is involved in glucose homeostasis and insulin sensitivity. - Neurodegenerative diseases, particularly through its involvement in amyloid-beta clearance and cellular responses to glucose stimuli. - Developmental biology, as it contributes to growth and differentiation processes during development.

Top Products

For researchers investigating IGF1R, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-IGF1 Receptor antibody (ab39675), which has garnered 62 citations and is particularly effective in Western blotting (WB) and immunohistochemistry (IHC). In addition, we offer the top-selling recombinant antibody, Anti-IGF1 Receptor antibody [EPR19322] (ab182408). This monoclonal antibody has been validated in knockout models and is suitable for a broader range of applications, including WB, immunocytochemistry (ICC), flow cytometry (FC), and immunoprecipitation (IP). With 88 citations, it demonstrates strong reliability and is an excellent choice for researchers seeking consistent performance in their studies of IGF1R. The Human IGF1 Receptor ELISA Kit (ab275102) is a reliable option for researchers looking to measure IGF1R levels in their samples.

Abcam Product Citation Summary

The data indicates that IGF1R is being studied in various human and mouse cell types, particularly focusing on its role in metabolic pathways and receptor signalling. The use of multiple antibodies in Western blotting suggests a robust interest in understanding the regulation and function of IGF1R in different biological contexts.

Abcam Product Citation Table

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.

Involvement in disease

Insulin-like growth factor 1 resistance

IGF1RES

A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner; Tyr-1165 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1161 and Tyr-1166. While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1165, Tyr-1161 and Tyr-1166) have to be phosphorylated for optimal activity. Can be autophosphorylated at additional tyrosine residues (in vitro). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines. Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding. Phosphorylation of Ser-1278 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1282. Dephosphorylated by PTPN1 (By similarity).

Polyubiquitinated at Lys-1168 and Lys-1171 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation.

Sumoylated with SUMO1.

Controlled by regulated intramembrane proteolysis (RIP). Undergoes metalloprotease-dependent constitutive ectodomain shedding to produce a membrane-anchored 52 kDa C-Terminal fragment which is further processed by presenilin gamma-secretase to yield an intracellular 50 kDa fragment.

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Tissue Specificity

Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney.

Cellular localization

• Cell membrane
• Single-pass type I membrane protein

Alternative names

CD221, Insulin-like growth factor 1 receptor, Insulin-like growth factor I receptor, IGF-I receptor, IGF1R

Database links

swissprot:P08069 entrezGene:3480 omim:147670 omim:147370 swissprot:P06213 entrezGene:3643

Other research areas

• Immuno-oncology