PMID- 9094314
OWN - NLM
STAT- MEDLINE
DCOM- 19970529
LR  - 20220330
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 7
IP  - 4
DP  - 1997 Apr 1
TI  - Characterization of a 3-phosphoinositide-dependent protein kinase which 
      phosphorylates and activates protein kinase Balpha.
PG  - 261-9
AB  - BACKGROUND: Protein kinase B (PKB), also known as c-Akt, is activated rapidly 
      when mammalian cells are stimulated with insulin and growth factors, and much of 
      the current interest in this enzyme stems from the observation that it lies 
      'downstream' of phosphoinositide 3-kinase on intracellular signalling pathways. 
      We recently showed that insulin or insulin-like growth factor 1 induce the 
      phosphorylation of PKB at two residues, Thr308 and Ser473. The phosphorylation of 
      both residues is required for maximal activation of PKB. The kinases that 
      phosphorylate PKB are, however, unknown. RESULTS: We have purified 500 000-fold 
      from rabbit skeletal muscle extracts a protein kinase which phosphorylates 
      PKBalpha at Thr308 and increases its activity over 30-fold. We tested the kinase 
      in the presence of several inositol phospholipids and found that only low 
      micromolar concentrations of the D enantiomers of either phosphatidylinositol 
      3,4,5-triphosphate (PtdIns(3,4,5)P3) or PtdIns(3,4)P2 were effective in potently 
      activating the kinase, which has been named PtdIns(3,4,5)P3-dependent protein 
      kinase-1 (PDK1). None of the inositol phospholipids tested activated or inhibited 
      PKBalpha or induced its phosphorylation under the conditions used. PDK1 activity 
      was not affected by wortmannin, indicating that it is not likely to be a member 
      of the phosphoinositide 3-kinase family. CONLCUSIONS: PDK1 is likely to be one of 
      the protein kinases that mediate the activation of PKB by insulin and growth 
      factors. PDK1 may, therefore, play a key role in mediating many of the actions of 
      the second messenger(s) PtdIns(3,4, 5)P3 and/or PtdIns(3,4)P2.
FAU - Alessi, D R
AU  - Alessi DR
AD  - Medical Research Council Protein Phosphorylation Unit, Department of 
      Biochemistry, University of Dundee, Dundee, DD1 4HN, Scotland. 
      dralessi@bad.dundee.ac.uk
FAU - James, S R
AU  - James SR
FAU - Downes, C P
AU  - Downes CP
FAU - Holmes, A B
AU  - Holmes AB
FAU - Gaffney, P R
AU  - Gaffney PR
FAU - Reese, C B
AU  - Reese CB
FAU - Cohen, P
AU  - Cohen P
LA  - eng
SI  - GENBANK/AF017995
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (PDPK1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis
MH  - Cell Line
MH  - Chromatography, Affinity
MH  - Chromatography, Ion Exchange
MH  - Enzyme Activation
MH  - Female
MH  - Humans
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Muscle, Skeletal/*enzymology
MH  - Peptide Fragments/chemistry/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/isolation & purification/*metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rabbits
MH  - Recombinant Fusion Proteins/metabolism
MH  - Serine
MH  - Substrate Specificity
MH  - Threonine
MH  - Transfection
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
AID - S0960-9822(06)00122-9 [pii]
AID - 10.1016/s0960-9822(06)00122-9 [doi]
PST - ppublish
SO  - Curr Biol. 1997 Apr 1;7(4):261-9. doi: 10.1016/s0960-9822(06)00122-9.