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.
Leslie
Nick R
NR
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
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