The inhibition of p85αPI3KSer83 phosphorylation prevents cell proliferation and invasion in prostate cancer cells.

Phosphoinositide 3-kinase proteins are composed by a catalytic p110 subunit and a regulatory p85 subunit. There are three classes of PI3K, named class I-III, on the bases of the protein domain constituting and determining their specificity. The first one is the best characterized and includes a number of key elements for the integration of different cellular signals. Regulatory p85 subunit shares with the catalytic p110 subunit, a N-terminal SH3 domain showing homology with the protein domain Rho-GTP-ase. After cell stimulation, all class I PI3Ks are recruited to the inner face of the plasma membrane, where they generate phosphatidylinositol-3,4,5-trisphosphate by direct phosphorylation of phosphatidylinositol-4,5-bisphosphate. All pathways trigger the control of different phenomena such as cell growth, proliferation, apoptosis, adhesion and migration through various downstream effectors. We have previously provided direct evidences that a Serine in position 83, adjacent to the N-terminal SH3 domain of regulatory subunit of PI3K, is a substrate of PKA. The aim of this work is to confirm the role of p85αPI3KSer83 in regulating cell proliferation, migration and invasion in prostate cancer cells LNCaP. To this purpose cells were transfected with mutant forms of p85, where Serine was replaced by Alanine, where phosphorylation is prevented, or Aspartic Acid, to mimic the phosphorylated residue. The findings of this study suggest that identifying a peptide mimicking the sequence adjacent to Ser 83 may be used to produce antibodies against this residue that can be proposed as usefool tool for prognosis by correlating phosphorylation at Ser83 with tumor stage.