PMID- 10026192
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 9
DP  - 1999 Feb 26
TI  - Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and
      co-localization with somatostatin in islet delta cells.
PG  - 5723-30
AB  - Phosphorylation of eukaryotic translation initiation factor-2alpha (eIF-2alpha)
      is one of the key steps where protein synthesis is regulated in response to
      changes in environmental conditions. The phosphorylation is carried out in part
      by three distinct eIF-2alpha kinases including mammalian double-stranded
      RNA-dependent eIF-2alpha kinase (PKR) and heme-regulated inhibitor kinase (HRI), 
      and yeast GCN2. We report the identification and characterization of a related
      kinase, PEK, which shares common features with other eIF-2alpha kinases including
      phosphorylation of eIF-2alpha in vitro. We show that human PEK is regulated by
      different mechanisms than PKR or HRI. In contrast to PKR or HRI, which are
      dependent on autophosphorylation for their kinase activity, a point mutation that
      replaced the conserved Lys-614 with an alanine completely abolished the
      eIF-2alpha kinase activity, whereas the mutant PEK was still autophosphorylated
      when expressed in Sf-9 cells. Northern blot analysis indicates that PEK mRNA was 
      predominantly expressed in pancreas, though low expression was also present in
      several tissues. Consistent with the high levels of mRNA in pancreas, the PEK
      protein was only detected in human pancreatic islets, and the kinase co-localized
      with somatostatin, a pancreatic delta cell-specific hormone. Thus PEK is believed
      to play an important role in regulating protein synthesis in the pancreatic
      islet, especially in islet delta cells.
FAU - Shi, Y
AU  - Shi Y
AD  - Diabetes Research, DC 0545, Endocrine Division, Lilly Research Laboratories, Eli 
      Lilly and Company, Indianapolis, Indiana 46285, USA. Shi_Yuguang@Lilly.com
FAU - An, J
AU  - An J
FAU - Liang, J
AU  - Liang J
FAU - Hayes, S E
AU  - Hayes SE
FAU - Sandusky, G E
AU  - Sandusky GE
FAU - Stramm, L E
AU  - Stramm LE
FAU - Yang, N N
AU  - Yang NN
LA  - eng
SI  - GENBANK/AF110146
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Complementary)
RN  - 51110-01-1 (Somatostatin)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Caenorhabditis elegans/genetics
MH  - DNA, Complementary
MH  - Humans
MH  - Islets of Langerhans/*enzymology
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Point Mutation
MH  - Rats
MH  - Sequence Homology, Amino Acid
MH  - Somatostatin/*metabolism
MH  - eIF-2 Kinase/genetics/*metabolism
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - 10.1074/jbc.274.9.5723 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Feb 26;274(9):5723-30. doi: 10.1074/jbc.274.9.5723.