Cell Signaling Technology

Product Pathways - Akt Signaling

Phospho-FoxO4 (Ser193) Antibody #9471

Applications Reactivity MW (kDa) Source
W H M Hm 70 Rabbit

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

Specificity / Sensitivity

Phospho-Fox04 (Ser193) Antibody detects endogenous levels of Fox04 only when phosphorylated at serine 193. The antibody may detect phospho-Fox01 at 82 kDa.

Source / Purification

Polyclonal antibodies are produced by immunizing rabbits with a synthetic phospho-peptide (KLH-coupled) corresponding to residues surrounding Ser256 of human Fox01. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from Cos cells, serum-starved or with serum treatment, using Phospho-Fox04 (Ser193) Antibody.

IHC-FL (floating)

IHC-FL (floating)

Confocal images of double immunostaining with Phospho-Fox04 (Ser193) Antibody (green) and propidium iodide (red) in rat hippocampal CA1 regions from tissue sections of control and 15 minute transient cerebral ischemia followed by 30 mintues of reperfusion. Yellow represents overlay of red and green. (Provided by Dr. Bingren Hu, University of Miami School of Medicine, Florida.)

Background

The Forkhead family of transcription factors is involved in tumorigenesis of rhabdomyosarcoma and acute leukemias (1-3). Within the family, three members (FoxO1, FoxO4 and FoxO3a) have sequence similarity to the nematode orthologue DAF-16, which mediates signaling via a pathway involving IGFR1, PI3K and Akt (4-6). Active forkhead members act as tumor suppressors by promoting cell cycle arrest and apoptosis. Increased expression of any FoxO member results in the activation of the cell cycle inhibitor p27Kip1. Forkhead transcription factors also play a part in TGF-β-mediated upregulation of p21CIP1, a process negatively regulated through PI3K (7). Increased proliferation results when forkhead transcription factors are inactivated through phosphorylation by Akt at Thr24, Ser256 and Ser319, which results in nuclear export and inhibition of transcription factor activity (8). Forkhead transcription factors can also be inhibited by the deacetylase sirtuin (SirT1) (9).

  1. Anderson, M.J. et al. (1998) Genomics 47, 187-199.
  2. Galili, N. et al. (1993) Nat. Genet. 5, 230-235.
  3. Borkhardt, A. et al. (1997) Oncogene 14, 195-202.
  4. Nakae, J. et al. (1999) J. Biol. Chem. 274, 15982-15985.
  5. Rena, G. et al. (1999) J. Biol. Chem. 274, 17179-17183.
  6. Guo, S. et al. (1999) J. Biol. Chem. 274, 17184-17192.
  7. Seoane, J. et al. (2004) Cell 117, 211-223.
  8. Arden, K.C. (2004) Mol. Cell 14, 416-418.
  9. Yang, Y. et al. (2005) EMBO J. 24, 1021-1032.

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