title: Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: E E
authors.initials: EE
authors.lastname: Vincent
authors.forename: D J E
authors.initials: DJ
authors.lastname: Elder
authors.forename: E C
authors.initials: EC
authors.lastname: Thomas
authors.forename: L
authors.initials: L
authors.lastname: Phillips
authors.forename: C
authors.initials: C
authors.lastname: Morgan
authors.forename: J
authors.initials: J
authors.lastname: Pawade
authors.forename: M
authors.initials: M
authors.lastname: Sohail
authors.forename: M T
authors.initials: MT
authors.lastname: May
authors.forename: M R
authors.initials: MR
authors.lastname: Hetzel
authors.forename: J M
authors.initials: JM
authors.lastname: Tavaré
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor; D013912:Threonine; D012694:Serine; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt