S6K: Ribosomal protein S6 kinase (vertebrates) p70S6 kinase αI and αII (p70 S6Kp85 S6K)

Abstract

The chapter discusses the S6Ks that from different mammalian species have amino acid sequence identities of >99%. A partial sequence covering the catalytic domain of Xenopus laevis S6K is 97% identical to mammalian S6K. The catalytic domain of mammalian S6K has 49% identity to Ypkl from Saccharomyces cerevisiae. Two isoforms of S6K are activated by phosphorylation in cells stimulated to proliferate. The kinase phosphorylates five serines near the C-terminus of ribosomal protein S6. S6 phosphorylation is implicated in the obligatory increase in protein synthesis required for the G0/G1 transition of the cell cycle. The only difference between the isoforms is that p85 contains 23 extra residues at the N-terminus, containing a nuclear localization signal (NLS). A single gene gives rise to four transcripts, two of which have been cloned. One clone encodes p70, the second encodes both forms. In the regulatory domain are four SP/TP motifs, which are phosphorylated following mitogenic stimulation of quiescent cells. These sites lie close to one another, in a putative autoinhibitory domain that has homology to the substrate recognition motif of S6.