PMID- 10491192
OWN - NLM
STAT- MEDLINE
DCOM- 19991122
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 265
IP  - 1
DP  - 1999 Oct 1
TI  - Molecular cloning, expression and characterization of the human serine/threonine 
      kinase Akt-3.
PG  - 353-60
AB  - Akt (also known as PKB or RAC-PK) is an intracellular serine/threonine kinase
      involved in regulating cell survival. Although this makes it a promising target
      for the discovery of drugs to treat human cancer, a complicating factor may be
      the role played by Akt in insulin signalling. Two human isoforms, Akt-1 and
      Akt-2, have been described previously and a third isoform has been identified in 
      rats (here termed Akt-3, but also called RAC-PK-gamma or PKB-gamma). We describe 
      the identification of the corresponding human isoform of Akt-3. The gene encoding
      human Akt-3 was localized to chromosome 1q43-44. The predicted protein sequence
      is 83% identical to human Akt-1 and 78% identical to human Akt-2, and contains a 
      pleckstrin homology domain and a kinase domain. In contrast to the published rat 
      Akt-3 isoform, human and mouse Akt-3 also possess a C-terminal 'tail' that
      contains a phosphorylation site (Ser472) thought to be involved in the activation
      of Akt kinases. In addition to phosphorylation of Ser472, phosphorylation of
      Thr305 also appears to contribute to the activation of Akt-3 because mutation of 
      both these residues to aspartate increased the catalytic activity of Akt-3,
      whereas mutation to alanine inhibited activation. Akt-3 activity could be
      inhibited by the broad spectrum kinase inhibitor staurosporine and by the PKC
      inhibitor Ro 31-8220, but not by other PKC or PKA inhibitors tested. Although
      Akt-3 is expressed widely, it is not highly expressed in liver or skeletal
      muscle, suggesting that its principle function may not be in regulating insulin
      signalling. These observations suggest that Akt-3 is a promising target for the
      discovery of novel chemotherapeutic agents which do not interfere with insulin
      signalling.
FAU - Masure, S
AU  - Masure S
AD  - Department of Biotechnology, Janssen Research Foundation, Beerse, Belgium.
FAU - Haefner, B
AU  - Haefner B
FAU - Wesselink, J J
AU  - Wesselink JJ
FAU - Hoefnagel, E
AU  - Hoefnagel E
FAU - Mortier, E
AU  - Mortier E
FAU - Verhasselt, P
AU  - Verhasselt P
FAU - Tuytelaars, A
AU  - Tuytelaars A
FAU - Gordon, R
AU  - Gordon R
FAU - Richardson, A
AU  - Richardson A
LA  - eng
SI  - GENBANK/AJ245709
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Indoles)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.1 (AKT3 protein, human)
RN  - EC 2.7.11.1 (Akt3 protein, mouse)
RN  - EC 2.7.11.1 (Akt3 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - H88EPA0A3N (Staurosporine)
RN  - W9A0B5E78O (Ro 31-8220)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 1
MH  - Cloning, Molecular
MH  - Enzyme Activation
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Indoles/pharmacology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Oncogene Proteins/antagonists & inhibitors/biosynthesis/*genetics
MH  - Protein Isoforms/biosynthesis/genetics
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors/biosynthesis/*genetics
MH  - Proto-Oncogene Proteins c-akt
MH  - RNA, Messenger/isolation & purification
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Homology, Amino Acid
MH  - Staurosporine/pharmacology
MH  - Tissue Distribution
EDAT- 1999/09/22 00:00
MHDA- 1999/09/22 00:01
CRDT- 1999/09/22 00:00
PHST- 1999/09/22 00:00 [pubmed]
PHST- 1999/09/22 00:01 [medline]
PHST- 1999/09/22 00:00 [entrez]
AID - ejb774 [pii]
AID - 10.1046/j.1432-1327.1999.00774.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1999 Oct 1;265(1):353-60. doi: 10.1046/j.1432-1327.1999.00774.x.