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Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.
Mol Cell Biol. 2003 Jul; 23(14):4796-804.MC

Abstract

Stimulation of the Ras/extracellular signal-regulated kinase (ERK) pathway can modulate cell growth, proliferation, survival, and motility. The p90 ribosomal S6 kinases (RSKs) comprise a family of serine/threonine kinases that lie at the terminus of the ERK pathway. Efficient RSK activation by ERK requires its interaction through a docking site located near the C terminus of RSK, but the regulation of this interaction remains unknown. In this report we show that RSK1 and ERK1/2 form a complex in quiescent HEK293 cells that transiently dissociates upon mitogen stimulation. Complex dissociation requires phosphorylation of RSK1 serine 749, which is a mitogen-regulated phosphorylation site located near the ERK docking site. Using recombinant RSK1 proteins, we find that serine 749 is phosphorylated by the N-terminal kinase domain of RSK1 in vitro, suggesting that ERK1/2 dissociation is mediated through RSK1 autophosphorylation of this residue. Consistent with this hypothesis, we find that inactivating mutations in the RSK1 kinase domains disrupted the mitogen-regulated dissociation of ERK1/2 in vivo. Analysis of different RSK isoforms revealed that RSK1 and RSK2 readily dissociate from ERK1/2 following mitogen stimulation but that RSK3 remains associated with active ERK1/2. RSK activity assays revealed that RSK3 also remains active longer than RSK1 and RSK2, suggesting that prolonged ERK association increased the duration of RSK3 activation. These results provide new evidence for the regulated nature of ERK docking interactions and reveal important differences among the closely related RSK family members.

Authors+Show Affiliations

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12832467

Citation

Roux, Philippe P., et al. "Phosphorylation of P90 Ribosomal S6 Kinase (RSK) Regulates Extracellular Signal-regulated Kinase Docking and RSK Activity." Molecular and Cellular Biology, vol. 23, no. 14, 2003, pp. 4796-804.
Roux PP, Richards SA, Blenis J. Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity. Mol Cell Biol. 2003;23(14):4796-804.
Roux, P. P., Richards, S. A., & Blenis, J. (2003). Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity. Molecular and Cellular Biology, 23(14), 4796-804.
Roux PP, Richards SA, Blenis J. Phosphorylation of P90 Ribosomal S6 Kinase (RSK) Regulates Extracellular Signal-regulated Kinase Docking and RSK Activity. Mol Cell Biol. 2003;23(14):4796-804. PubMed PMID: 12832467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity. AU - Roux,Philippe P, AU - Richards,Stephanie A, AU - Blenis,John, PY - 2003/7/2/pubmed PY - 2003/8/15/medline PY - 2003/7/2/entrez SP - 4796 EP - 804 JF - Molecular and cellular biology JO - Mol. Cell. Biol. VL - 23 IS - 14 N2 - Stimulation of the Ras/extracellular signal-regulated kinase (ERK) pathway can modulate cell growth, proliferation, survival, and motility. The p90 ribosomal S6 kinases (RSKs) comprise a family of serine/threonine kinases that lie at the terminus of the ERK pathway. Efficient RSK activation by ERK requires its interaction through a docking site located near the C terminus of RSK, but the regulation of this interaction remains unknown. In this report we show that RSK1 and ERK1/2 form a complex in quiescent HEK293 cells that transiently dissociates upon mitogen stimulation. Complex dissociation requires phosphorylation of RSK1 serine 749, which is a mitogen-regulated phosphorylation site located near the ERK docking site. Using recombinant RSK1 proteins, we find that serine 749 is phosphorylated by the N-terminal kinase domain of RSK1 in vitro, suggesting that ERK1/2 dissociation is mediated through RSK1 autophosphorylation of this residue. Consistent with this hypothesis, we find that inactivating mutations in the RSK1 kinase domains disrupted the mitogen-regulated dissociation of ERK1/2 in vivo. Analysis of different RSK isoforms revealed that RSK1 and RSK2 readily dissociate from ERK1/2 following mitogen stimulation but that RSK3 remains associated with active ERK1/2. RSK activity assays revealed that RSK3 also remains active longer than RSK1 and RSK2, suggesting that prolonged ERK association increased the duration of RSK3 activation. These results provide new evidence for the regulated nature of ERK docking interactions and reveal important differences among the closely related RSK family members. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/12832467/Phosphorylation_of_p90_ribosomal_S6_kinase__RSK__regulates_extracellular_signal_regulated_kinase_docking_and_RSK_activity_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=12832467 DB - PRIME DP - Unbound Medicine ER -