Phospho-IGF-IR (Y1161) Polyclonal Antibody, 100 µg, (ATB-P0138)

Description

Background:

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.

Product datasheet:

References:

1. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity.
   Ullrich A., Gray A., Tam A.W., Yang-Feng T., Tsubokawa M., Collins C., Henzel W., Bon T.L., Kathuria S., Chen E., Jacobs S., Francke U., Ramachandran J., Fujita-Yamaguchi Y.
   EMBO J. 5:2503-2512(1986) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-56; 446-453; 503-524; 561-579; 668-672 AND 721-729. Tissue: Placenta.
2. Insulin-like growth factor I receptor gene structure.
   Abbot A.M., Bueno R., Pedrini M.T., Murray J.M., Smith R.J.
   J. Biol. Chem. 267:10759-10763(1992) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
3. Nagase T., Kikuno R.F., Yamakawa H., Ohara O.
   Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databasesCited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Fetal brain.
4. NIEHS SNPs program
   Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databasesCited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-388 AND HIS-605.
5. Analysis of the DNA sequence and duplication history of human chromosome 15.
   Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O’Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
   , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O’Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
   Nature 440:671-675(2006) [PubMed] [Europe PMC]

   Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

6. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
   The MGC Project Team
   Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
7. Analysis of the human type I insulin-like growth factor receptor promoter region.
   Cooke D.W., Bankert L.A., Roberts C.T. Jr., Leroith D., Casella S.J.
   Biochem. Biophys. Res. Commun. 177:1113-1120(1991) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31.
8. Characterization of human placental insulin-like growth factor-I/insulin hybrid receptors by protein microsequencing and purification.
   Kasuya J., Paz I.B., Maddux B.A., Goldfine I.D., Hefta S.A., Fujita-Yamaguchi Y.
   Biochemistry 32:13531-13536(1993) [PubMed] [Europe PMC] Cited for: PROTEIN SEQUENCE OF 31-45 AND 741-750, FUNCTION, FORMATION OF A HYBRID RECEPTOR WITH INSR. Tissue: Placenta.
9. A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes.
   Lee S.-T., Strunk K.M., Spritz R.A.
   Oncogene 8:3403-3410(1993) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1137-1193, TISSUE SPECIFICITY. Tissue: Melanocyte.
10. Interaction of the alpha beta dimers of the insulin-like growth factor I receptor is required for receptor autophosphorylation.
    Tollefsen S.E., Stoszek R.M., Thompson K.
    Biochemistry 30:48-54(1991) [PubMed] [Europe PMC] Cited for: FUNCTION, SUBUNIT, AUTOPHOSPHORYLATION.