PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase
- 1 July 1994
- journal article
- Published by Springer Nature in Nature
- Vol. 370 (6484) , 71-75
- https://doi.org/10.1038/370071a0
Abstract
Platelet-derived growth factor receptor (PDGF-R) phosphorylation at tyrosines 740/751 and insulin receptor phosphorylation of insulin receptor substrate-1 effects the recruitment and activation of phosphatidylinositol-3-OH kinase (PI(3)K). Changes in PI(3)K activity correlate with cell growth but its downstream signal transducers are unknown. Activation of the 70/85K S6 kinases (pp70S6k) by serine phosphorylation results in 40S ribosomal protein S6 phosphorylation and is important for G1 cell-cycle transition in a variety of cells. Although receptor tyrosine kinases activate the microtubule-associated protein kinase cascade through SH2-/SH3-adaptor proteins, Sos and c-Ras, it is unclear how tyrosine kinases are coupled to the pp70S6k phosphorylation cascade. Here we report that PI(3)K mediates PDGF or insulin receptor signalling to pp70S6k. PI(3)K-mediated activation of pp70S6k is independent of conventional protein kinase C isoforms. Additionally, rapamycin blocks pp70S6k activation by all mitogens, without inhibiting PI(3)K, and acts downstream in this signalling system.Keywords
This publication has 28 references indexed in Scilit:
- p70s6k function is essential for G1 progressionNature, 1993
- Rapamycin-Induced Inhibition of the 70-Kilodalton S6 Protein KinaseScience, 1992
- Activation of p70s6k is associated with phosphorylation of four clustered sites displaying Ser/Thr-Pro motifs.Proceedings of the National Academy of Sciences, 1992
- Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinaseNature, 1992
- GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct regions of the platelet-derived growth factor receptor beta subunit.Molecular and Cellular Biology, 1992
- Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinasesCell, 1992
- Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathwaysCell, 1992
- Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction proteinNature, 1991
- Phosphoinositide kinasesBiochemistry, 1990
- Molecular structure of a major insulin/mitogen-activated 70-kDa S6 protein kinase.Proceedings of the National Academy of Sciences, 1990