Characterization of a mutant pancreatic eIF-2α kinase, PEK, and co- localization with somatostatin in islet delta cells

Yuguang Shit, Jie An, Jingdong Liang, Scott E. Hayes, George E. Sandusky, Lawrence E. Stramm, Na N. Yang

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Phosphorylation of eukaryotic translation initiation factor-2α (eIF- 2α) 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-2α kinases including mammalian double-stranded RNA-dependent elF-2α 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 elF-2α kinases including phosphorylation of eIF-2α 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-2α 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.

Original languageEnglish (US)
Pages (from-to)5723-5730
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number9
DOIs
StatePublished - Feb 26 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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