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. shows that hybrid receptors composed of IGF1R and INSR isoform Longare 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 Shortare activated by IGF1, IGF2 and insulin. In contrast, shows that hybrid receptors composed of IGF1R and INSR isoform Longand hybrid receptors composed of IGF1R and INSR isoform Shorthave similar binding characteristics, both bind IGF1 and have a low affinity for insulin.Ullrich A.EMBO J. 5:2503-2512(1986).Abbot A.M.,J. Biol. Chem. 267:10759-10763(1992).The MGC Project Team;Genome Res. 14:2121-2127(2004).
Host
Rabbit
Immunogen
Synthesized non-phosphopeptide derived from Human IGF1R around the phosphorylation site of tyrosine 1346 (Q-P-Y(p)-A-H).
Involvement In Disease
Insulin-like growth factor 1 resistance (IGF1RES)
Raised In
Rabbit
Reactivity
Human, Mouse
Regulatory
RUO
Relevance
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. shows that hybrid receptors composed of IGF1R and INSR isoform Longare 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 Shortare activated by IGF1, IGF2 and insulin. In contrast, shows that hybrid receptors composed of IGF1R and INSR isoform Longand hybrid receptors composed of IGF1R and INSR isoform Shorthave similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
Ullrich A.EMBO J. 5:2503-2512(1986). Abbot A.M.,J. Biol. Chem. 267:10759-10763(1992). The MGC Project Team;Genome Res. 14:2121-2127(2004).
Species
Homo Sapiens (Human)
Specificity
The antibody detects endogenous levels of total IGF1R protein.
Subcellular Location
Cell membrane, Single-pass type I membrane protein
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
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
Buffer
Rabbit IgG in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Form
Rabbit IgG in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Format
liquid
Purification
The antibody was affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogen.
Purity
The antibody was affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogen.
Storage
Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.