Anti-Insulin-like Growth Factor 1 Receptor Antibody, Non-Fucosylated (BioBet-1035ZP) (CAT#: BioBet-1035ZP) Datasheet

IGF1R

insulin-like growth factor 1 receptor

This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

IGF1R; insulin-like growth factor 1 receptor; IGFR; CD221; IGFIR; JTK13; IGF-I receptor; soluble IGF1R variant 1; soluble IGF1R variant 2; insulin-like growth factor I receptor

Plasma membrane

Diseases associated with IGF1R include Insulin-Like Growth Factor I and Ring Chromosome 15.

Its related pathways are Apoptosis Modulation and Signaling and Transcriptional misregulation in cancer.

Receptor tyrosine kinase mediates the action of insulin-like growth factor 1 (IGF1). High affinity binds IGF1, low affinity binds IGF2 and insulin (INS). Activated IGF1R is involved in the control of cell growth and survival. IGF1R is essential for tumor transformation and survival of malignant cells. Ligand binding activates receptor kinases, leading to receptor autophosphorylation and tyrosine phosphorylation of multiple substrates, which act as signal transduction adaptor proteins, including insulin receptor substrates (IRS1/2), Shc and 14 -3-3 protein. Phosphorylation of IRSs protein leads to the activation of two main signal pathways: PI3K-AKT/PKB pathway and Ras-MAPK pathway. Activating the MAPK pathway results in increased cell proliferation, while activating the PI3K pathway inhibits cell apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), thereby activating multiple downstream substrates, including the protein AKT/PKB. Phosphorylation of AKT in turn promotes protein synthesis by activating mTOR, and triggers the anti-apoptotic effect of IGFIR by phosphorylation and inactivation of BAD. Simultaneously with the signaling pathway driven by pi3k, the recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to the recruitment of Ras and the activation of the Ras-mapk pathway. In addition to these two main signal pathways, IGF1R signals are also transmitted through Janus kinase/signal converters and transcription pathway activators (JAK/STAT). The phosphorylation of JAK protein can lead to phosphorylation/activation of signal transducer and transcription (STAT) protein. In particular, the activation of STAT3 may be crucial to the transformation activity of IGF1R. JAK/STAT pathway activates gene transcription, which may be related to transformation activity. JNK kinase can also be activated by IGF1R. IGF1 inhibits the activation of JNK through phosphorylation and inhibition of MAP3K5/ASK1, and MAP3K5/ASK1 can directly bind to IGF1R.

Cancer antibody; Developmental Biology antibody; Neuroscience antibody; Signaling Transduction antibody

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.

Protein Based Therapies
Monoclonal antibody (mAb)

IgG

EM164

Humanized

Human

AVE1642 is an anti-insulin-like growth factor-1 receptor (IGF-1R/CD221) monoclonal antibody, administered as a single agent and in combination with docetaxel in patients with advanced solid tumours.

Cancer; Multiple Myeloma

Cancer; Multiple Myeloma