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

Antonia Feola, Annamaria Cimini, Francesca Migliucci, Rosamaria Iorio, Candida Zuchegna, Rodger Rothenberger, Letizia Cito, Antonio Porcellini, Gerhard Unteregger, Vincenzo Tombolini, Antonio Giordano, Marina Di Domenico

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2114-2119
Number of pages6
JournalJournal of Cellular Biochemistry
Volume114
Issue number9
DOIs
Publication statusPublished - 2013

Fingerprint

Phosphorylation
Cell proliferation
Phosphatidylinositol 3-Kinases
Prostatic Neoplasms
src Homology Domains
Cells
Cell Proliferation
Phosphatidylinositols
Serine
Catalytic Domain
1-Phosphatidylinositol 4-Kinase
Cell growth
Cell membranes
Guanosine Triphosphate
Aspartic Acid
Alanine
Protein Kinases
Cell Movement
Tumors
Proteins

Keywords

  • LnCap
  • PHOSPHORYLATION
  • PROSTATE CANCER
  • REGULATORY SUBUNIT p85

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Feola, A., Cimini, A., Migliucci, F., Iorio, R., Zuchegna, C., Rothenberger, R., ... Di Domenico, M. (2013). The inhibition of p85αPI3KSer83 phosphorylation prevents cell proliferation and invasion in prostate cancer cells. Journal of Cellular Biochemistry, 114(9), 2114-2119. https://doi.org/10.1002/jcb.24558

The inhibition of p85αPI3KSer83 phosphorylation prevents cell proliferation and invasion in prostate cancer cells. / Feola, Antonia; Cimini, Annamaria; Migliucci, Francesca; Iorio, Rosamaria; Zuchegna, Candida; Rothenberger, Rodger; Cito, Letizia; Porcellini, Antonio; Unteregger, Gerhard; Tombolini, Vincenzo; Giordano, Antonio; Di Domenico, Marina.

In: Journal of Cellular Biochemistry, Vol. 114, No. 9, 2013, p. 2114-2119.

Research output: Contribution to journalArticle

Feola, A, Cimini, A, Migliucci, F, Iorio, R, Zuchegna, C, Rothenberger, R, Cito, L, Porcellini, A, Unteregger, G, Tombolini, V, Giordano, A & Di Domenico, M 2013, 'The inhibition of p85αPI3KSer83 phosphorylation prevents cell proliferation and invasion in prostate cancer cells', Journal of Cellular Biochemistry, vol. 114, no. 9, pp. 2114-2119. https://doi.org/10.1002/jcb.24558
Feola, Antonia ; Cimini, Annamaria ; Migliucci, Francesca ; Iorio, Rosamaria ; Zuchegna, Candida ; Rothenberger, Rodger ; Cito, Letizia ; Porcellini, Antonio ; Unteregger, Gerhard ; Tombolini, Vincenzo ; Giordano, Antonio ; Di Domenico, Marina. / The inhibition of p85αPI3KSer83 phosphorylation prevents cell proliferation and invasion in prostate cancer cells. In: Journal of Cellular Biochemistry. 2013 ; Vol. 114, No. 9. pp. 2114-2119.
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