Abstract
The eukaryotic protein kinase (ePK) paradigm provides integral components for signal transduction cascades throughout nature. However, while so-called typical ePKs permeate the Eucarya and Bacteria, atypical ePKs dominate the kinomes of the Archaea. Intriguingly, the catalytic domains of the handful of deduced typical ePKs from the archaeon Sulfolobus solfataricus 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 S. solfataricus homolog of eIF2α, aIF2α. The activity of SsoPK4 was inhibited in vitro by 3ʹ,5ʹ-cyclic AMP (Ki of ~23 µM) and was activated by oxidized Coenzyme A, an indicator of oxidative stress in the Archaea. Activation enhanced the apparent affinity for protein substrates, Km, but had little effect on Vmax. Autophosphorylation activated SsoPK4 and rendered it insensitive to oxidized Coenzyme A.
Highlights
Covalent phosphorylation constitutes nature’s most versatile and extensible mechanism for modulating the structural and functional properties of proteins [1,2,3]
The hyperthermophilic archaeon S. solfataricus contains more than five hundred proteins that are phosphorylated on serine, threonine, and/or tyrosine residues [24]
Its genome [25] encodes several potential protein kinases, three of which conform to the typical eukaryotic protein kinase (ePK) paradigm: open reading frames (ORF) sso2291, sso3182, and sso3207 [26]
Summary
Covalent phosphorylation constitutes nature’s most versatile and extensible mechanism for modulating the structural and functional properties of proteins [1,2,3]. Among the families of enzymes that catalyze this important covalent modification event, the most prolific by far are the so-called “typical” eukaryotic protein kinases (ePKs) [4]. It was of considerable interest that as genome sequences continued to be accumulated, that open reading frames (ORF) encoding deduced typical ePKs were encountered in members of the Archaea, within the creanarchaeal branch of this domain. The catalytic domains of the putative archaeal members of the typical ePK family bear a discernable resemblance to the set of typical ePKs responsible for phosphorylating eukaryotic translational initiation factor 2α (eIF2α). In the Eucarya, the eIF2α kinases phosphorylate and inactivate eIF2α in response to indicators of stress such as amino acid limitation, viral infection, unfolded proteins, etc. 3',5'-cAMP and oxidized Coenzyme A, an indicator of oxidative stress, upon its catalytic activity
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