cDNA encoding a 59 kDa homolog of ribosomal protein S6 kinase from rabbit liver

Abstract

We have isolated cDNA molecules encoding a protein with the characteristic sequence elements that are conserved between the catalytic domains of protein kinases. This protein is apparently a serine/threonine kinase and is most closely related to the amino-terminal half of the ribosomal protein S6 kinase II first characterized in Xenopus eggs (42% overall identity and 56% identity in the predicted catalytic domain). However, it clearly differs from S6 kinase II in that it has only one, rather than two predicted catalytic domains and a deduced molecular mass of 59 109 Da. We propose that is may be more related to, or identical with, the mitogen-inducible S6 kinase of molecular mass 65-70 kDa described in mammalian liver, mouse 3T3 cells and chicken embryos. Remarkable structural features of the cDNA-encoded polypeptide are a section rich in proline, serine and threonine residues that resemble the multiphosphorylation domains of glycogen synthase and phosphorylase kinase a subunit, and a characteristic tyrosine residue in the putative nucleotide-binding glycine cluster which, by analogy to cdc2 kinase, is a potential tyrosine phosphorylation site.

Nuclear localization of p85s6k: functional requirement for entry into S phase.

“…Consistent with these results, the unique 23 amino acid extension of rat p85s6k contains two possible nuclear localization motifs (Dingwall and Laskey, 1991;Garcia-Bustos et al, 1991): the classical SV40 targeting sequence and the recently described bipartite nuclear targeting motif. The bipartite nuclear targeting sequence is not conserved in rabbit and human p85s6k (Harmann and Kilimann, 1990;Grove et al, 1991) and, thus, nuclear localization is most likely conferred by the first cluster of basic amino acids, Arg2-Arg7. Site-directed mutagenesis studies should resolve which of these motifs is being employed to direct p85s6k to the nucleus (Cochrane et al, 1990).…”

A single gene encodes two isoforms of the p70 S6 kinase: activation upon mitogenic stimulation.

“…Clone 2 was 2.3 kb and contained a short (21 nt) 5' untranslated region followed by a "weak" consensus translation start site and an open reading frame capable of encoding a 525-amino acid protein. A cDNA clone almost identical to clone 2 has also been isolated from a rabbit cDNA library (21). A second AUG start codon in clone 2 has been identified at nt 91 (19), which corresponds to the strong translation start site of clone 1 (18).…”

Clinical potential of the mTOR effectors S6K1, S6K2 and 4EBP1 in breast cancer

“…However, subsequent studies led to the discovery of the p70 ribosomal S6 kinase, as the major S6 kinase in somatic cells [126,127]. The RPS6KB1 gene, encoding S6K1, was first cloned in rat and rabbit [128][129][130] and shortly after the human orthologue located at the chromosomal region 17q23, was discovered and shown to encode two splicing variants, p70 and p85S6K1 [131]. At the end of the 1990s, a close paralogue of S6K1, termed S6K2, was cloned by several groups [132][133][134][135].…”