GCKIII (Germinal Center Kinase III) Kinases STK24 and STK25 (Serine/Threonine Kinase 24 and 25) Inhibit Cavernoma Development.

Background: Cavernous cerebral malformations can arise because of mutations in the , , or genes, and lack of has also been reported to induce these malformations in mice. However, the role of the CCM3 (cerebral cavernous malformation 3)-associated kinases in cavernoma development is not known, and we, therefore, have investigated their role in the process.

Methods: We used a combination of an in vivo approach, using mice genetically modified to be deficient in the CCM3-associated kinases STK24 and STK25 (serine/threonine kinases 24 and 25), and the in vitro model of human endothelial cells in which expression of and was inhibited by RNA interference.

High Levels of Receptor Tyrosine Kinases in CCM3-Deficient Cells Increase Their Susceptibility to Tyrosine Kinase Inhibition.

Cerebral cavernous malformations (CCMs) are vascular malformations that can be the result of the deficiency of one of the CCM genes. Their only present treatment is surgical removal, which is not always possible, and an alternative pharmacological strategy to eliminate them is actively sought. We have studied the effect of the lack of one of the CCM genes, CCM3, in endothelial and non-endothelial cells.

MST Kinases and Metabolism.

Since the discovery of the mammalian sterile twenty (MST) kinase family of proteins (MST1/STK4, MST2/STK3, MST3/STK24, and SOK1/STK25), much has been done that adds to our knowledge of their structure, regulation, and function. In the last few years, a series of articles has unveiled a previous unknown relation of these kinases with metabolic regulation and the homeostasis of metabolic tissues. The aim of this review is to bring together this body of data to provide a detailed picture of the current knowledge about these proteins, metabolism, and some of the associated diseases.

The MST3/STK24 kinase mediates impaired fasting blood glucose after a high-fat diet.

Aims/hypothesis: The identification of mediators in the pathogenesis of type 2 diabetes mellitus is essential for the full understanding of this disease. Protein kinases are especially important because of their potential as pharmacological targets. The goal of this study was to investigate whether mammalian sterile-20 3 (MST3/STK24), a stress-regulated kinase, is involved in metabolic alterations in obesity.