PMID- 10364160
OWN - NLM
STAT- MEDLINE
DCOM- 19990727
LR  - 20211203
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 11
DP  - 1999 Jun 1
TI  - A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals 
      that regulate diapause in Caenorhabditis elegans.
PG  - 1438-52
AB  - An insulin receptor-like signaling pathway regulates Caenorhabditis elegans
      metabolism, development, and longevity. Inactivation of the insulin receptor
      homolog DAF-2, the AGE-1 PI3K, or the AKT-1 and AKT-2 kinases causes a
      developmental arrest at the dauer stage. A null mutation in the daf-16 Fork head 
      transcription factor alleviates the requirement for signaling through this
      pathway. We show here that a loss-of-function mutation in pdk-1, the C. elegans
      homolog of the mammalian Akt/PKB kinase PDK1, results in constitutive arrest at
      the dauer stage and increased life span; these phenotypes are suppressed by a
      loss of function mutation in daf-16. An activating mutation in pdk-1 or
      overexpression of wild-type pdk-1 relieves the requirement for AGE-1 PI3K
      signaling. Therefore, pdk-1 activity is both necessary and sufficient to
      propagate AGE-1 PI3K signals in the DAF-2 insulin receptor-like signaling
      pathway. The activating mutation in pdk-1 requires akt-1 and akt-2 gene activity 
      in order to suppress the dauer arrest phenotype of age-1. This indicates that the
      major function of C. elegans PDK1 is to transduce signals from AGE-1 to AKT-1 and
      AKT-2. The activating pdk-1 mutation is located in a conserved region of the
      kinase domain; the equivalent amino acid substitution in human PDK1 activates its
      kinase activity toward mammalian Akt/PKB.
FAU - Paradis, S
AU  - Paradis S
AD  - Department of Molecular Biology, Massachusetts General Hospital, Department of
      Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
FAU - Ailion, M
AU  - Ailion M
FAU - Toker, A
AU  - Toker A
FAU - Thomas, J H
AU  - Thomas JH
FAU - Ruvkun, G
AU  - Ruvkun G
LA  - eng
SI  - GENBANK/AF130406
SI  - GENBANK/AF130407
GR  - R01 AG014161/AG/NIA NIH HHS/United States
GR  - R01 CA075134/CA/NCI NIH HHS/United States
GR  - R01AG14161/AG/NIA NIH HHS/United States
GR  - R01CA75134/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Helminth Proteins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.1.137 (AGE-1 protein, C elegans)
RN  - EC 2.7.10.1 (DAF-2 protein, C elegans)
RN  - EC 2.7.10.1 (Receptor, Insulin)
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 (AKT2 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)
RN  - EC 2.7.11.1 (akt-1 protein, C elegans)
RN  - EC 2.7.11.1 (akt-2 protein, C elegans)
RN  - HG18B9YRS7 (Valine)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - Alanine
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Animals
MH  - Caenorhabditis elegans/*enzymology/genetics/*physiology
MH  - *Caenorhabditis elegans Proteins
MH  - Enzyme Activation
MH  - Gene Expression Regulation, Enzymologic
MH  - Green Fluorescent Proteins
MH  - Helminth Proteins/*metabolism
MH  - Humans
MH  - Luminescent Proteins/genetics
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Phenotype
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptor, Insulin/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - *Signal Transduction
MH  - Valine
PMC - PMC316759
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1101/gad.13.11.1438 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Jun 1;13(11):1438-52. doi: 10.1101/gad.13.11.1438.