Identification of Xenopus S6 protein kinase homologs (pp90rsk) in somatic cells: phosphorylation and activation during initiation of cell proliferation.
We have identified human, mouse, and chicken homologs to Xenopus S6 protein kinase II (S6KII). In quiescent cells, the apparent molecular mass of the Xenopus homologs (referred to as pp90rsk) increased from a range of 81 to 91 to a range of 85 to 92 kilodaltons following serum addition, which is consistent with an increase in protein phosphorylation. Indeed, serum growth factors stimulated pp90rsk phosphorylation at multiple serine and threonine residues. Furthermore, pp90rsk activity was stimulated within seconds of serum addition. Distinct molecular sizes, chromatographic properties, phosphopeptide maps, and kinetics of activation, the lack of immunological cross-reactivity, and analysis of S6 kinase activities in cells that overexpressed pp90rsk suggest that pp90rsk and pp70-S6 protein kinase, a previously identified mitogen- and oncogene-regulated S6 kinase in cultured cells, are distinct and differentially regulated. The notion that both enzymes are regulated by protein phosphorylation was supported by the ability to inactivate their S6 phosphotransferase activities with potato acid phosphatase. These data demonstrate that homologs to the Xenopus S6 protein kinases are produced and regulated by protein phosphorylation in somatic cells and that, in addition to a proposed role in Xenopus oocyte maturation, these homologs may participate in the initiation of animal cell proliferation.
Chen
R H
RH
Department of Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611.
Blenis
J
J
D000135:Acid Phosphatase; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D003429:Cross Reactions; D005347:Fibroblasts / Q000201:enzymology; D015870:Gene Expression; D006367:HeLa Cells / Q000201:enzymology; D007106:Immune Sera; D051379:Mice; D008970:Molecular Weight; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases; D012689:Sequence Homology, Nucleic Acid; D014357:Trypsin; D014981:Xenopus
D007106:Immune Sera; D010748:Phosphopeptides; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D000135:Acid Phosphatase; D014357:Trypsin