Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons
Stephanie zur Nedden,
Serine/threonine protein kinase C-related kinase (PKN/PRK) is a family of three isoenzymes (PKN1, PKN2,
PKN3), which are widely distributed in eukaryotic organisms and share the same overall domain structure. The Nterminal
region encompasses a conserved repeated domain, termed HR1a-c as well as a HR2/C2 domain. The
serine/threonine kinase domain is found in the C-terminal region of the protein and shows high sequence homology to
other members of the PKC superfamily.
In neurons, PKN1 is the most abundant isoform and has been implicated in a variety of functions including cytoskeletal
organization and neuronal differentiation and its deregulation may contribute to neuropathological processes such as
amyotrophic lateral sclerosis and Alzheimer’s disease. We have recently identified a candidate role of PKN1 in the
regulation of neuroprotective processes during hypoxic stress. Our key findings were that: 1) the activity of PKN1 was
significantly increased by hypoxia (1% O2) and neurotrophins (nerve growth factor and purine nucleosides); 2) Neuronal
cells, deficient of PKN1 showed a decrease of cell viability and neurite formation along with a disturbance of the F-actinassociated
cytoskeleton; 3) Purine nucleoside-mediated neuroprotection during hypoxia was severely hampered in PKN1
deficient neuronal cells, altogether suggesting a potentially critical role of PKN1 in neuroprotective processes.
This review gives an up-to-date overview of the PKN family with a special focus on the neuroprotective role of PKN1 in
Keywords: Hypoxia, neuroprotection, PKN, PRK, protein kinase C-related kinase, purine nucleosides, review.
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