Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase β containing a proline-rich region

A novel ribosomal S6 kinase, termed p70 S6 kinase beta (p70 beta), which has a highly conserved amino acid sequence compared with that of p70/p85 S6 kinase (p70 alpha) within the catalytic, kinase extension, and autoinhibitory pseudosubstrate domains, was identified. However, the amino acid sequence of p70 beta differs from that of p70 alpha in the noncatalytic amino-terminal region and in the carboxyl-terminal tail, which contains a proline-rich region. The majority of the regulatory phosphorylation sites identified in p70 alpha are conserved in p70 beta, Two isoforms of p70 beta, referred to as pi (495 amino acids) and beta 2 (482 amino acids), could be expressed from the single gene either by alternative mRNA splicing or by the use of alternative start codons. Here we report the characterization of p70 beta 2. Similarly to p70 alpha, the catalytic activity of p70 beta toward ribosomal protein S6 could be rapidly activated by serum, insulin, and phorbol ester in transiently transfected cells. The p70 beta kinase was found to be significantly less sensitive to wortmannin and rapamycin than p70 alpha. These results indicate that p70 beta has the potential to participate in the regulation of protein synthesis and the cell cycle.