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Identification of regulated genes during permanent focal cerebral ischaemia: characterization of the protein kinase 9b5/MARKL1/MARK4
Ist Teil von
Journal of neurochemistry, 2004-03, Vol.88 (5), p.1114-1126
Ort / Verlag
Oxford, UK: Blackwell Science Ltd
Erscheinungsjahr
2004
Link zum Volltext
Quelle
Wiley Online Library Journals Frontfile Complete
Beschreibungen/Notizen
Cerebral ischaemia induces transcriptional changes in a number of pathophysiologically important genes. Here we have systematically studied gene expression changes after 90 min and 24 h of permanent focal ischaemia in the mouse by an advanced fragment display technique (restriction‐mediated differential display). We identified 56 transcriptionally altered genes, many of which provide novel hints to ischaemic pathophysiology. Particularly interesting were two pro‐apoptotic genes (Grim19 and Tdag51), whose role in cerebral ischaemia and neuronal cell death has not been recognized so far. Among the unknown sequences, we identified a gene that was rapidly and transiently up‐regulated. The encoded protein displayed high homology to the MARK family of serine–threonine protein kinases and has recently been described as MARKL1/MARK4. Here we demonstrate that this protein is a functional protein kinase with the ability to specifically phosphorylate a cognate peptide substrate for the AMP‐kinase family. Upon overexpression in heterologous cells, the functional wild‐type protein, but not its kinase‐dead mutant, led to decreased cell viability. We conclude that the up‐regulation of this kinase during focal ischaemia may represent an interesting new target for pharmacological intervention.