Identification of regulated genes during permanent focal cerebral ischaemia: Characterization of the protein kinase 9b5/MARKL1/MARK4

Armin Schneider*, Rico Laage, Oliver Von Ahsen, Achim Fischer, Moritz Rossner, Sigrid Scheek, Sylvia Grünewald, Rohini Kuner, Daniela Weber, Carola Krüger, Bettina Klaussner, Bernhard Götz, Holger Hiemisch, Dieter Newrzella, Ana Martin-Villalba, Alfred Bach, Markus Schwaninger

*Corresponding author for this work
34 Citations (Scopus)


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.

Original languageEnglish
JournalJournal of Neurochemistry
Issue number5
Pages (from-to)1114-1126
Number of pages13
Publication statusPublished - 01.03.2004

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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