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RSK activation

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-444257

PubChem

R-HSA-444257

Description

Ribosomal S6 kinase (RSK) has four isoforms in humans, RPS6KA1 (RSK1), RPS6KA2 (RSK3), RPS6KA3 (RSK2) and RPS6KA6 (RSK4), and each of the isoforms have six conserved phosphorylation sites (in RPS6KA1, these are serine residues S221, S363 and S380 and threonine residues T359, T573 and T732). Phosphorylation at four of these residues appears to be critically important for the catalytic activity of RSKs: S221, S363, S380 and T573 (in RPS6KA1).
Phosphorylation and activation of RSKs primarily occurs at the plasma membrane, but can occur in the cytoplasm and in the nucleus. ERKs (MAPK1 and MAPK3), activated downstream of RAS signaling, phosphorylate RSKs on threonine and serine residues T359, S363 and T573 (in RPS6KA1). Phosphorylation by ERKs enables autophosphorylation of RSKs on serine residue S380 and threonine residue T732 (in RPS6KA1). Phosphorylation of RSKs by PDPK1 (PDK1) at serine residue S221 (in RPS6KA1) is necessary for the full activation of RSKs and phosphorylation of RSK substrates (reviewed by Anjum and Blenis 2012). RSK4 differs from other RSKs because it shows high level of constitutive phosphorylation and activity in the absence of growth factors, although it is still responsive to growth factors and ERK activity (Dummler et al. 2005).
RSKs, especially RSK2, are highly expressed in brain regions with high synaptic activity. RSK2 mutations are the underlying cause of Coffin-Lowry syndrome (CLS), which is characterized by cognitive impairment and skeletal anomalies (Zeniou et al. 2002).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 3** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O15530	3-phosphoinositide-dependent protein kinase 1	PDK1 PDPK1	view
P51812	Ribosomal protein S6 kinase alpha-3	ISPK1 MAPKAPK1B RPS6KA3 RSK2	view
Q15418	Ribosomal protein S6 kinase alpha-1	MAPKAPK1A RPS6KA1 RSK1	view

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