PTEN/PI3K/Akt/VEGF signaling and the cross talk to KRIT1, CCM2, and PDCD10 proteins in cerebral cavernous malformations.
Cerebral cavernous malformations (CCM) are common vascular malformation of the brain and are associated with abnormal angiogenesis. Although the exact etiology and the underlying molecular mechanism are still under investigation, recent advances in the identification of the mutations in three genes and their interactions with different signaling pathways have shed light on our understanding of CCM pathogenesis. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is known to play a major role in angiogenesis. Studies have shown that the phosphatase and tensin homologue deleted on chromosome ten (PTEN), a tumor suppressor, is an antagonist regulator of the PI3K/Akt pathway and mediates angiogenesis by activating vascular endothelial growth factor (VEGF) expression. Here, we provide an update literature review on the current knowledge of the PTEN/PI3K/Akt/VEGF signaling in angiogenesis, more importantly in CCM pathogenesis. In addition to reviewing the current literatures, this article will also focus on the structural domain of the three CCM proteins and their interacting partners. Understanding the biology of these proteins with respect to their signaling counterpart will help to guide future research towards new therapeutic targets applicable for CCM treatment.
International Neuroscience Institute, Rudolf-Pichlmayr-Straße 4, 30625, Hannover, Germany, kar@ini-hannover.de.
Souvik
S
Kar
Amir
A
Samii
Helmut
H
Bertalanffy
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D020786:Hemangioma, Cavernous, Central Nervous System / Q000378:metabolism*; D006801:Humans; D000075927:KRIT1 Protein; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human