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Signaling pathways involved in eIF4B Ser422 phosphorylation. Growth factor-activated MAPK and PI3K cascades activate RSK and S6K proteins correspondingly and converge at the level of eIF4B phosphorylation. In systems where insulin is a marginal activator (dashed arrow) of MAPK cascade, insulin-induced eIF4B phosphorylation is absolutely sensitive to rapamycin. PDK1 protein plays a central role in activation of both RSK and S6K proteins and is indispensable for eIF4B phosphorylation.
