S6 phosphorylation and the p70s6k/p85s6k

Area of Science:

• Molecular Biology
• Cell Signaling
• Biochemistry

Background:

• Cell growth activation involves 40S ribosomal protein S6 phosphorylation.
• The p70s6k/p85s6k kinase is responsible for this event, with distinct cytoplasmic and nuclear isoforms.
• The signaling pathway for p70s6k/p85s6k activation is not fully understood and differs from p21ras and p42mapk/p44mapk pathways.

Purpose of the Study:

• To elucidate the signaling pathway leading to p70s6k/p85s6k activation.
• To investigate the role of phosphatidyl-inositol-3-OH kinase and alternative routes in this pathway.
• To understand the mechanism by which rapamycin affects p70s6k activation and mRNA translation.

Main Methods:

• Utilizing point mutants of the PDGF receptor.
• Employing inhibitors of phosphatidyl-inositol-3-OH kinase.
• Treating cells with the immunosuppressant rapamycin.

Main Results:

• The p70s6k/p85s6k pathway appears distinct from p21ras and p42mapk/p44mapk pathways.
• Phosphatidyl-inositol-3-OH kinase is implicated, but alternative signaling routes may exist.
• Rapamycin inhibits p70s6k activation, S6 phosphorylation, and translation of mRNAs with a 5' polypyrimidine tract.

Conclusions:

• The p70s6k/p85s6k signaling pathway is complex and influenced by factors like rapamycin.
• Rapamycin's inhibition of S6 phosphorylation impacts the translation of specific mRNAs.
• Phosphorylated S6 may directly or indirectly interact with the polypyrimidine tract on mRNAs.