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.
- Cell Transformation, Neoplastic
- GTPase-Activating Proteins
- Guanine Nucleotide Exchange Factors
- PTEN Phosphohydrolase
- Phosphatidylinositol 3-Kinases
- Point Mutation
- Signal Transduction