A model for dynamic phosphorylation and dephosphorylation of rpS6 C terminus. A, initiation and maintenance of rpS6 phosphorylation. Upon mitogenic stimulation, p90 RSK and p70 S6K kinase families phosphorylate Ser-235/236. Ser-235/236 phosphorylation (circled P) promotes p70 S6K-dependent phosphorylation of Ser-240 and Ser-244. Ser-244 phosphorylation then promotes CK1-dependent phosphorylation of Ser-247. Phospho-Ser-247 triggers feedback phosphorylation of Ser-240/244, which sustains rpS6 phosphorylation and its association with the 5′-m7GpppG cap complex. B, dephosphorylation of rpS6 by PP1. After cessation of mitogenic stimuli and inactivation of rpS6 kinases, PP1 rapidly dephosphorylates rpS6 beginning with Ser-247. Unphosphorylated rpS6 then dissociates from the 5′-m7GpppG cap complex. A and B, circled P indicates phosphorylation. Phosphorylation sites are underlined.