Product Pathways - Translational Control

p70 S6 Kinase (49D7) Rabbit mAb #2708

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Applications	Reactivity	Sensitivity	MW (kDa)	Isotype
W IHC-P	H M R Mk	Endogenous	70, 85	Rabbit IgG

Applications Key:  W=Western Blotting  IHC-P=Immunohistochemistry (Paraffin)
Reactivity Key:  H=Human  M=Mouse  R=Rat  Mk=Monkey
Species cross-reactivity is determined by Western blot.

Specificity / Sensitivity

p70 S6 Kinase (49D7) Rabbit mAb detects endogenous levels of total p70 S6 kinase protein. The antibody also recognizes p85 S6 kinase.

Source / Purification

Monoclonal antibodies are produced by immunizing rabbits with a synthetic peptide (KLH-coupled) derived from residues surrounding the amino-terminus of human p70 S6 kinase.

Background

p70 S6 kinase is a mitogen activated Ser/Thr protein kinase that is required for cell growth and G1 cell cycle progression (1,2). p70 S6 kinase phosphorylates the S6 protein of the 40S ribosomal subunit and is involved in translational control of 5' oligopyrimidine tract mRNAs (1). A second isoform, p85 S6 kinase, is derived from the same gene and is identical to p70 S6 kinase except for 23 extra residues at the amino terminus, which encode a nuclear localizing signal (1). Both isoforms lie on a mitogen activated signaling pathway downstream of phosphoinositide-3 kinase (PI-3K) and the target of rapamycin, FRAP/mTOR, a pathway distinct from the Ras/MAP kinase cascade (1). The activity of p70 S6 kinase is controlled by multiple phosphorylation events located within the catalytic, linker and pseudosubstrate domains (1). Phosphorylation of Thr229 in the catalytic domain and Thr389 in the linker domain are most critical for kinase function (1). Phosphorylation of Thr389, however, most closely correlates with p70 kinase activity in vivo (3). Prior phosphorylation of Thr389 is required for the action of phosphoinositide 3-dependent protein kinase 1 (PDK1) on Thr229 (4,5). Phosphorylation of this site is stimulated by growth factors such as insulin, EGF and FGF, as well as by serum and some G-protein-coupled receptor ligands, and is blocked by wortmannin, LY294002 (PI-3K inhibitor) and rapamycin (FRAP/mTOR inhibitor) (1,6,7). Ser411, Thr421 and Ser424 lie within a Ser-Pro-rich region located in the pseudosubstrate region (1). Phosphorylation at these sites is thought to activate p70 S6 kinase via relief of pseudosubstrate suppression (1,2). Another LY294002 and rapamycin sensitive phosphorylation site, Ser371, is an in vitro substrate for mTOR and correlates well with the activity of a partially rapamycin resistant mutant p70 S6 kinase (8).

1. Pullen, N. and Thomas, G. (1997) FEBS Lett. 410, 78-82.
2. Dufner, A. and Thomas, G. (1999) Exp. Cell Res. 253, 100-109.
3. Weng, Q.P. et al. (1998) J. Biol. Chem. 273, 16621-16629.
4. Pullen, N. et al. (1998) Science 279, 707-710.
5. Alessi, D.R. et al. (1998) Curr. Biol. 8, 69-81.
6. Polakiewicz, R.D. et al. (1998) J. Biol. Chem. 273, 23534-23541.
7. Fingar, D.C. et al. (2002) Genes Dev. 16, 1472-1487.
8. Saitoh, M. et al. (2002) J. Biol. Chem. 277, 20104-20112.

Application References

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Companion Products

• 9202 p70 S6 Kinase Antibody
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• 9206 Phospho-p70 S6 Kinase (Thr389) (1A5) Mouse mAb
• 9208 Phospho-p70 S6 Kinase (Ser371) Antibody
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• 1205 p70 S6 Kinase Blocking Peptide
• 9234 Phospho-p70 S6 Kinase (Thr389) (108D2) Rabbit mAb

Rabbit Monoclonals Produced Using Epitomics® Technology, U.S. Patent No. 5,675,063.

This product is for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.