RAS/ERK Signaling Promotes Site-specific Ribosomal Protein S6 Phosphorylation via RSK and Stimulates Cap-dependent Translation

摘要: Converging signals from the mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K) pathways are well established to modulate translation initiation. Less is known regarding molecular basis protein synthesis regulated by other inputs, such as agonists Ras/extracellular signal-regulated kinase (ERK) signaling cascade. Ribosomal (rp) S6 a component 40S ribosomal subunit that becomes phosphorylated at several serine residues upon mitogen stimulation, but exact mechanisms regulating its phosphorylation function rpS6 poorly understood. Here, we provide evidence activation p90 kinases (RSKs) serum, growth factors, tumor promoting phorbol esters, oncogenic Ras required for downstream Ras/ERK We demonstrate while 1 (S6K1) phosphorylates all sites, RSK exclusively Ser235/236 in vitro vivo using an mTOR-independent mechanism. Mutation reveals these sites promotes recruitment 7-methylguanosine cap complex, suggesting regulates assembly preinitiation complex. These data provides pathway linking cascade translational machinery.