Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region.
A novel ribosomal S6 kinase, termed p70 S6 kinase beta (p70beta), which has a highly conserved amino acid sequence compared with that of p70/p85 S6 kinase (p70alpha) within the catalytic, kinase extension, and autoinhibitory pseudosubstrate domains, was identified. However, the amino acid sequence of p70beta differs from that of p70alpha 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 p70alpha are conserved in p70beta. Two isoforms of p70beta, referred to as beta1 (495 amino acids) and beta2 (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 p70beta2. Similarly to p70alpha, the catalytic activity of p70beta toward ribosomal protein S6 could be rapidly activated by serum, insulin, and phorbol ester in transiently transfected cells. The p70beta kinase was found to be significantly less sensitive to wortmannin and rapamycin than p70alpha. These results indicate that p70beta has the potential to participate in the regulation of protein synthesis and the cell cycle.
Gout
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Ludwig Institute for Cancer Research, London W1P 8BY and the Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom. ivan@ludwig.ucl.ac.uk
Minami
T
T
Hara
K
K
Tsujishita
Y
Y
Filonenko
V
V
Waterfield
M D
MD
Yonezawa
K
K
D000595:Amino Acid Sequence; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D016466:CHO Cells; D020134:Catalytic Domain / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010449:Peptide Mapping; D010766:Phosphorylation; D011392:Proline / Q000032:analysis*; D019893:Ribosomal Protein S6 Kinases / Q000737:chemistry / Q000235:genetics*; D020123:Sirolimus / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D011392:Proline; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D000077191:Wortmannin