Ribosomal S6 kinase 1 (RSK1) activation requires signals dependent on and independent of the MAP kinase ERK

Abstract

RSK1 is phosphorylated by PDK1 in the amino-terminal kinase-activation loop, and by ERK in the carboxy-terminal kinase-activation loop. Activation of phosphotransferase activity of full-length RSK1 in vivo requires both PDK1 and ERK. RSK1 activation is therefore regulated by both the mitogen-stimulated ERK/MAP kinase pathway and a PDK1-dependent pathway.

The C-terminal Kinase and ERK-binding Domains of Drosophila S6KII (RSK) Are Required for Phosphorylation of the Protein and Modulation of Circadian Behavior

“…ERK is thought to initiate the sequential phosphorylation of multiple S6KII residues by binding to a specific docking domain at the terminus of the protein, resulting in phosphorylation of residue T732 (and perhaps also S498) (T573 and S363 in RSK, respectively) and subsequent activation of the C-terminal kinase (22)(23)(24). The C-terminal kinase autophosphorylates S515 (RSK S380), creating a binding site for PDK1, which then docks and phosphorylates S6KII S357 (RSK S221), activating the N-terminal kinase domain and enabling the phosphorylation of S6KII target substrates (14,(25)(26)(27).…”

Critical role for Rsk2 in T-lymphocyte activation

“…Full catalytic activity of Rsks requires activation by both extracellular signal-regulated kinase (ERK) 21,22 and PDK1 (3-phosphoinositide-dependent protein kinase 1). 23,24 Rsk family kinases have multiple cellular functions. They are involved in the phosphorylation of histone H3 and remodeling of chromatin in response to epidermal growth factor (EGF) 25 and can regulate gene expression by phosphorylating transcription factors, including c-Fos, 26,27 cAMP-response element-binding protein (CREB), [28][29][30] CREB-binding protein, 31,32 estrogen receptor, 33 ATF4,34 NFATc4, 35 and NF-B/I B␣.…”

p90 Ribosomal S6 Kinase 1 (RSK1) and the Catalytic Subunit of Protein Kinase A (PKA) Compete for Binding the Pseudosubstrate Region of PKAR1α

“…The activated CTK then autophosphorylates the RSKs to permit docking of PDK1 that then phosphorylates a Ser residue (Ser-221 in rat RSK1) in the activation loop of the NTK (11). The fully active RSKs, via their NTK, then phosphorylate their respective substrates (12). The fully active RSK1 and RSK2 are also translocated to the nucleus where they phosphorylate several transcription factors to mediate their biological actions (13).…”