P-REX2a driving tumorigenesis by PTEN inhibition.
The phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10) antagonizes phosphoinositide 3-kinase (PI3K) signaling and is one of the most frequently mutated tumor suppressors in human cancers. Its regulation appears complex and is of great potential clinical importance. The protein P-REX2a (phosphatidylinositol 3,4,5-trisphosphate Rac exchanger 2a), better known as a regulator of the small guanosine triphosphatase Rac, has been identified as a direct regulator of PTEN activity and as a potential oncoprotein. P-REX2a can stimulate cell proliferation by inhibiting PTEN and stimulating downstream PI3K-dependent signaling. This suggests that aberrant control of PTEN by P-REX2a may represent a key tumorigenic mechanism, in agreement with recent studies supporting the pathological relevance of several other proposed PTEN regulators.
Division of Molecular Physiology, College of Life Sciences, University of Dundee, The James Black Centre, Dow Street, Dundee, DD1 5EH, UK. n.r.leslie@dundee.ac.uk
Nick R
NR
Leslie
D002471:Cell Transformation, Neoplastic; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017354:Point Mutation; D015398:Signal Transduction
D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C490712:PREX2 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human