Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis

The regulated phosphorylation of ribosomal protein (rp) S6 has attracted much attention since its discovery in 1974, yet its physiological role has remained obscure. To directly address this issue, we have established viable and fertile knock-in mice, whose rpS6 contains alanine substitutions at all five phosphorylatable serine residues (rpS6(P-/-)). Here we show that contrary to the widely accepted model, this mutation does not affect the translational control of TOP mRNAs. rpS6(P-/-) mouse embryo fibroblasts (MEFs) display an increased rate of protein synthesis and accelerated cell division, and they are significantly smaller than rpS6(P+/+) MEFs. This small size reflects a growth defect, rather than a…

• US
  United States-Israel Binational Science Foundation
• IS
  Israel Science Foundation