Anti-Insulin Receptor/INSR Antibody Picoband® Fluoro488 Conjugated

INSR (INSULIN RECEPTOR) is a tetramer of 2 alpha and 2 beta subunits that are coded by a single gene and are joined by disulfide bonds, a mechanism parallel to that of its ligand, insulin. It belongs to the large class of tyrosine kinase receptors. The insulin receptor gene is mapped to 19p13.2. The insulin receptor mediates their activity by causing the addition of a phosphate group to particular tyrosines on certain proteins within a cell. The INSR gene spans more than 120 kb and has 22 exons. Functional studies of the INSR SNPs show no effect on mRNA levels or splicing in peripheral blood leukocytes or on binding of insulin to mononuclear cells.

Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2) . The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2- antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1) . Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. .

1. Accili, D., Drago, J., Lee, E. J., Johnson, M. D., Cool, M. H., Salvatore, P., Asico, L. D., Jose, P. A., Taylor, S. I., Westphal, H. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nature Genet. 12: 106-109, 1996. 2. 't Hart, L. M., Stolk, R. P., Dekker, J. M., Nijpels, G., Grobbee, D. E., Heine, R. J., Maassen, J. A. Prevalence of variants in candidate genes for type 2 diabetes mellitus in the Netherlands: the Rotterdam study and the Hoorn study. J. Clin. Endocr. Metab. 84: 1002-1006, 1999. 3. Ward CW, Lawrence MC (April 2009) . Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor.

Cytoplasm. Cell membrane. Mitochondrion. Nucleus. Colocalizes with RGS14 and BRAF in both the cytoplasm and membranes. Phosphorylation at Ser-259 impairs its membrane accumulation. Recruited to the cell membrane by the active Ras protein. Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its mitochondrial localization. Retinoic acid- induced Ser-621 phosphorylated form of RAF1 is predominantly localized at the nucleus.