PMID- 10637513
OWN - NLM
STAT- MEDLINE
DCOM- 20000204
LR  - 20161124
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 56
DP  - 1999 Dec 23
TI  - Integrin-linked kinase regulates phosphorylation of serine 473 of protein kinase 
      B by an indirect mechanism.
PG  - 8024-32
AB  - The serine threonine kinase protein kinase B regulates cellular activities as
      diverse as glycogen metabolism and apoptosis. Full activation of protein kinase B
      requires 3-phosphoinositides and dual phosphorylation on threonine-308 and
      serine-473. CaM-K kinase and 3-phosphoinositide dependent-kinase-1 phosphorylate 
      threonine-308. Integrin-linked kinase reportedly phophorylates serine-473.
      Consistent with this, in a model COS cell system we show that expression of
      wild-type integrin-linked kinase promotes the wortmannin sensitive
      phosphorylation of serine-473 of protein kinase B and its downstream substrates, 
      and inhibits C2-ceramide induced apoptosis. In contrast, integrin-linked kinase
      mutated in a lysine residue critical for function in protein kinases is inactive 
      in these experiments, and furthermore, acts dominantly to block serine-473
      phosphorylation induced by ErbB4. However, alignment of analogous sequences from 
      different species demonstrates that integrin-linked kinase is not a typical
      protein kinase and identifies a conserved serine residue which potentially
      regulates kinase activity in a phosphorylation dependent manner. Mutation of this
      serine to aspartate or glutamate, but not alanine, in combination with the
      inactivating lysine mutation restores integrin-linked kinase dependent
      phosphorylation of serine-473 of protein kinase B. These data strongly suggest
      that integrin-linked kinase does not possess serine-473 kinase activity but
      functions as an adaptor to recruit a serine-473 kinase or phosphatase.
FAU - Lynch, D K
AU  - Lynch DK
AD  - Department of Pathology, Cambridge Unversity, Tennis Court Road, Cambridge CB2
      1QP, UK.
FAU - Ellis, C A
AU  - Ellis CA
FAU - Edwards, P A
AU  - Edwards PA
FAU - Hiles, I D
AU  - Hiles ID
LA  - eng
SI  - GENBANK/AJ249344
SI  - GENBANK/AJ249345
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 17885-08-4 (Phosphoserine)
RN  - EC 2.7.1.- (integrin-linked kinase)
RN  - EC 2.7.11.1 (Akt1 protein, Drosophila)
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 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.1 (akt-1 protein, C elegans)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Caenorhabditis elegans
MH  - Caenorhabditis elegans Proteins
MH  - Catalytic Domain
MH  - Drosophila Proteins
MH  - Drosophila melanogaster
MH  - Humans
MH  - Molecular Sequence Data
MH  - Phosphatidylinositols/metabolism
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Protein-Serine-Threonine Kinases/*chemistry/genetics/*metabolism
MH  - Proto-Oncogene Proteins/chemistry/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-raf/chemistry
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Transfection
EDAT- 2000/01/19 00:00
MHDA- 2000/01/19 00:01
CRDT- 2000/01/19 00:00
PHST- 2000/01/19 00:00 [pubmed]
PHST- 2000/01/19 00:01 [medline]
PHST- 2000/01/19 00:00 [entrez]
AID - 10.1038/sj.onc.1203258 [doi]
PST - ppublish
SO  - Oncogene. 1999 Dec 23;18(56):8024-32. doi: 10.1038/sj.onc.1203258.