A Goswami

A Slipicevic

AS Tsao

B Solomon

B Vanhaesebroeck

BD Manning

BR Balsara

C Morgan

D J E Elder

DA Altomare

DD Sarbassov

DL Dai

DR Alessi

E C Thomas

E E Vincent

EB Nascimento

G Perez-Tenorio

H Sun

J Feng

J Li

J M Tavaré

J Pawade

J Tsurutani

JM Tang

JN Andersen

JQ Cheng

KE O’Reilly

KM Geraghty

L Phillips

LC Cantley

LR Pearce

M Hanada

M R Hetzel

M Sohail

M T May

MM Hill

N Gallay

O David

OJ Shah

PP Massion

RC Hresko

S Kane

S Ramaswamy

SK Pal

SL Cai

T Mukohara

TL Yuan

WT Lim

YO Al-Bazz

English

PubMed

BACKGROUND: The activity of the protein kinase Akt is frequently dysregulated in cancer and is an important factor in the growth and survival of tumour cells. Akt activation involves the phosphorylation of two residues: threonine 308 (Thr308) in the activation loop and serine 473 (Ser473) in the C-terminal hydrophobic motif. Phosphorylation of Ser473 has been extensively studied in tumour samples as a correlate for Akt activity, yet the phosphorylation of Thr308 or of downstream Akt substrates is rarely assessed. METHODS: The phosphorylation status of Thr308 and Ser473 was compared with that of three separate Akt substrates - PRAS40, TSC2 and TBC1D4 - in fresh frozen samples of early-stage human non-small cell lung cancer (NSCLC). RESULTS: Akt Thr308 phosphorylation correlated with the phosphorylation of each Akt substrate tested, whereas Akt Ser473 phosphorylation did not correlate with the phosphorylation of any of the substrates examined. CONCLUSION: The phosphorylation of Thr308 is a more reliable biomarker for the protein kinase activity of Akt in tumour samples than Ser473. Any evaluation of the link between Akt phosphorylation or activity in tumour samples and the prediction or prognosis of disease should, therefore, focus on measuring the phosphorylation of Akt on Thr308 and/or at least one downstream Akt substrate, rather than Akt Ser473 phosphorylation alone.BACKGROUND: The activity of the protein kinase Akt is frequently dysregulated in cancer and is an important factor in the growth and survival of tumour cells. Akt activation involves the phosphorylation of two residues: threonine 308 (Thr308) in the activation loop and serine 473 (Ser473) in the C-terminal hydrophobic motif. Phosphorylation of Ser473 has been extensively studied in tumour samples as a correlate for Akt activity, yet the phosphorylation of Thr308 or of downstream Akt substrates is rarely assessed. METHODS: The phosphorylation status of Thr308 and Ser473 was compared with that of three separate Akt substrates - PRAS40, TSC2 and TBC1D4 - in fresh frozen samples of early-stage human non-small cell lung cancer (NSCLC). RESULTS: Akt Thr308 phosphorylation correlated with the phosphorylation of each Akt substrate tested, whereas Akt Ser473 phosphorylation did not correlate with the phosphorylation of any of the substrates examined. CONCLUSION: The phosphorylation of Thr308 is a more reliable biomarker for the protein kinase activity of Akt in tumour samples than Ser473. Any evaluation of the link between Akt phosphorylation or activity in tumour samples and the prediction or prognosis of disease should, therefore, focus on measuring the phosphorylation of Akt on Thr308 and/or at least one downstream Akt substrate, rather than Akt Ser473 phosphorylation alone

Vincent, E. E.

Elder, D. J E

Thomas, E. C.

Phillips, L.

Morgan, C.

Pawade, J.

Sohail, M.

May, M. T.

Hetzel, M. R.

Tavaré, J. M.

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Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer

Crossref

British Journal of Cancer

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Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Ba.

Immuno-analysis of phospho-Akt in primary human breast cancers.

Perturbations of the AKT signaling pathway in human cancer.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3111153

Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer

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