Cell Signaling Technology

Product Pathways - Glucose Metabolism

AS160 (C69A7) Rabbit mAb #2670

Applications Reactivity MW (kDa) Source Isotype
W IP H M R 160 Rabbit IgG

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human  M=Mouse  R=Rat
Species enclosed in parentheses are predicted to react based on 100% sequence homology. Species cross-reactivity is determined by Western blot.

Specificity / Sensitivity

AS160 (C69A7) Rabbit mAb detects endogenous levels of total AS160 protein.

Source / Purification

Monoclonal antibody is produced by immunizing rabbits with a synthetic peptide (KLH-coupled) derived from the sequence around Ala195 of human AS160.

Western Blotting

Western Blotting

Western blot analysis of extracts from HepG2, RD and 293T cells using AS160 (C69A7) Rabbit mAb.

Background

The polypeptide insulin is a major hormone controlling critical energy functions such as glucose and lipid metabolism. Insulin binds to and activates the insulin receptor (IR) tyrosine kinase, which phosphorylates and recruits different adaptor proteins. The signaling pathway initiated by insulin and its receptor stimulates glucose uptake in muscle cells and adipocytes through translocation of GLUT4 glucose transporters from the cytoplasm to the plasma membrane (1). A 160 kDa substrate of the Akt serine/threonine kinase (AS160, TBC1D4) is a Rab GTPase activating protein that regulates insulin-stimulated GLUT4 trafficking. AS160 is expressed in many tissues including brain, kidney, liver and brown and white fat (2). Multiple Akt phosphorylation sites were identified on AS160 in vivo, with five sites showing increased phosphorylation following insulin treatment (2,3). Studies using recombinant AS160 demonstrated that insulin-stimulated phosphorylation of AS160 is a crucial step in GLUT4 translocation (3) and is reduced in some patients with type 2 diabetes (4). The interaction of 14-3-3 regulatory proteins with AS160 phosphorylated at Thr642 is another necessary step for GLUT4 translocation (5). Phosphorylation of AS160 by AMPK is involved in the regulation of contraction-stimulated GLUT4 translocation (6).

  1. Watson, R.T. and Pessin, J.E. (2006) Trends Biochem. Sci. 31, 215-222.
  2. Kane, S. et al. (2002) J. Biol. Chem. 277, 22115-22118.
  3. Sano, H. et al. (2003) J. Biol. Chem. 278, 14599-14602.
  4. Karlsson, H.K. et al. (2005) Diabetes 54, 1692-1697.
  5. Ramm, G. et al. (2006) J. Biol. Chem. 281, 29174-29180.
  6. Kramer, H.F. et al. (2006) J. Biol. Chem. 281, 31478-31485.

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