PMID- 10226025
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 8
DP  - 1999 Apr 22
TI  - PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from
      the carboxyl terminus of PRK2.
PG  - 393-404
AB  - BACKGROUND: Protein kinase B (PKB) is activated by phosphorylation of Thr308 and 
      of Ser473. Thr308 is phosphorylated by the 3-phosphoinositide-dependent protein
      kinase-1 (PDK1) but the identity of the kinase that phosphorylates Ser473
      (provisionally termed PDK2) is unknown. RESULTS: The kinase domain of PDK1
      interacts with a region of protein kinase C-related kinase-2 (PRK2), termed the
      PDK1-interacting fragment (PIF). PIF is situated carboxy-terminal to the kinase
      domain of PRK2, and contains a consensus motif for phosphorylation by PDK2
      similar to that found in PKBalpha, except that the residue equivalent to Ser473
      is aspartic acid. Mutation of any of the conserved residues in the PDK2 motif of 
      PIF prevented interaction of PIF with PDK1. Remarkably, interaction of PDK1 with 
      PIF, or with a synthetic peptide encompassing the PDK2 consensus sequence of PIF,
      converted PDK1 from an enzyme that could phosphorylate only Thr308 of PKBalpha to
      one that phosphorylates both Thr308 and Ser473 of PKBalpha in a manner dependent 
      on phosphatidylinositol (3,4,5) trisphosphate (PtdIns(3,4,5)P3). Furthermore, the
      interaction of PIF with PDK1 converted the PDK1 from a form that is not directly 
      activated by PtdIns(3,4,5)P3 to a form that is activated threefold by
      PtdIns(3,4,5)P3. We have partially purified a kinase from brain extract that
      phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that 
      is immunoprecipitated with PDK1 antibodies. CONCLUSIONS: PDK1 and PDK2 might be
      the same enzyme, the substrate specificity and activity of PDK1 being regulated
      through its interaction with another protein(s). PRK2 is a probable substrate for
      PDK1.
FAU - Balendran, A
AU  - Balendran A
AD  - MRC Protein Phosphorylation Unit, Department of Biochemistry, University of
      Dundee, Dundee DD1 5EH, UK.
FAU - Casamayor, A
AU  - Casamayor A
FAU - Deak, M
AU  - Deak M
FAU - Paterson, A
AU  - Paterson A
FAU - Gaffney, P
AU  - Gaffney P
FAU - Currie, R
AU  - Currie R
FAU - Downes, C P
AU  - Downes CP
FAU - Alessi, D R
AU  - Alessi DR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Isoenzymes)
RN  - 0 (Lipids)
RN  - 0 (Peptides)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 1114-81-4 (Phosphothreonine)
RN  - 17885-08-4 (Phosphoserine)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.1.- (protein kinase N)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (PDPK1 protein, human)
RN  - EC 2.7.11.1 (Pdpk1 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Enzyme Activation
MH  - Glutathione Transferase/genetics
MH  - Humans
MH  - Isoenzymes/*metabolism
MH  - Lipids/physiology
MH  - Molecular Sequence Data
MH  - Peptides/chemical synthesis/genetics/*metabolism
MH  - Phosphatidylinositol Phosphates/physiology
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Phosphothreonine/metabolism
MH  - Protein Binding
MH  - Protein Kinase C/chemistry/genetics/*metabolism
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Saccharomyces cerevisiae/genetics
MH  - Sensitivity and Specificity
MH  - Sequence Homology, Amino Acid
MH  - Substrate Specificity
EDAT- 1999/05/05 00:00
MHDA- 1999/05/05 00:01
CRDT- 1999/05/05 00:00
PHST- 1999/05/05 00:00 [pubmed]
PHST- 1999/05/05 00:01 [medline]
PHST- 1999/05/05 00:00 [entrez]
AID - S0960-9822(99)80186-9 [pii]
AID - 10.1016/s0960-9822(99)80186-9 [doi]
PST - ppublish
SO  - Curr Biol. 1999 Apr 22;9(8):393-404. doi: 10.1016/s0960-9822(99)80186-9.