Molecular structure of a major insulin/mitogen-activated 70-kDa S6 protein kinase.

Abstract

The molecular structure of a rat hepatoma 70-kDa insulin/mitogen-stimulated S6 protein kinase, obtained by molecular cloning, is compared to that of a rat homolog of the 85-kDa Xenopus S6 protein kinase a; both kinases were cloned from H4 hepatoma cDNA libraries Most efforts at purification of mitogen-stimulated S6 kinase activity from avian and mammalian sources have recovered 65-to 70-kDa polypeptides (10-12). We purified an hepatic 70-kDa S6 kinase, activated by cycloheximide treatment of the rat; this very low abundance enzyme cochromatographed with the major hepatic S6 kinase activated during liver regeneration and after insulin treatment of H4 hepatoma cells (13). The latter enzyme was also purified extensively from 32P-labeled H4 hepatoma cells and found to correspond to a 70-kDa 32P-labeled polypeptide, which is phosphorylated on serine residues in response to insulin, concomitant with activation (5). Like the Xenopus S6 kinase II, the hepatic p70 S6 kinase is also deactivated by protein phosphatase 2A; these two S6 kinases, however, are immunochemically distinct (D.J.P., J.A., E. Erikson, and J.

The effects of the immunosuppressant rapamycin on the growth of rheumatoid arthritis (RA) synovial fibroblast

“…Two distinct families of growth factor-related S6 kinases, p70 S6 kinase and p90 rsk , have been identified [21,22]. Activation of these kinases by phosphorylation on serine and threonine residues resulted in 40S ribosomal protein S6 phosphorylation.…”

UVA Induces Ser381 Phosphorylation of p90RSK/MAPKAP-K1 via ERK and JNK Pathways

“…The two domains are the aminoterminal kinase domain (NTD) and the carboxyl-terminal kinase domain (CTD) (16,22). With regard to primary structure, the NTD of p90 RSK is most closely related to p70 S6 kinase (p70 S6K ) (16,23). It was shown to phosphorylate exogenous substrates for p90 RSK , including the cAMP response elementbinding protein (24), c-Fos (25), and the estrogen receptor (26).…”

IGF-I elicits growth of human intestinal smooth muscle cells by activation of PI3K, PDK-1, and p70S6 kinase

“…The initial step in p70S6 kinase activation involves the phosphorylation of serine/threonine residues in the autoinhibitory pseudosubstrate domain (Ser 411 , Ser 418 , Ser 424 , Ser 429 , and Thr 421 ) and in the catalytic domain extension (Thr 390 and Ser 394 ) under the control of proline-directed kinases (7,30). The result is the release of the autoinhibitory carboxy-terminal tail from the catalytic domain allowing access to Thr 229 and Thr 389 .…”