Activation of SsoPK4, an Archaeal eIF2α Kinase Homolog, by Oxidized CoA.

The eukaryotic protein kinase (ePK) paradigm provides integral components for signal transduction cascades throughout nature However, while so-called typical ePKs permeate the and atypical ePKs dominate the kinomes of the . Intriguingly, the catalytic domains of the handful of deduced typical ePKs from the archaeon P2 exhibit significant resemblance to the protein kinases that phosphorylate translation initiation factor 2α (eIF2α) in response to cellular stresses. We cloned and expressed one of these archaeal eIF2α protein kinases, SsoPK4. SsoPK4 exhibited protein-serine/threonine kinase activity toward several proteins, including the homolog of eIF2α, aIF2α. The activity of SsoPK4 was inhibited by 3',5'-cyclic AMP (K of ~23 µM) and was activated by oxidized Coenzyme A, an indicator of oxidative stress in the Activation enhanced the apparent affinity for protein substrates, K, but had little effect on V. Autophosphorylation activated SsoPK4 and rendered it insensitive to oxidized Coenzyme A.