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Review
. 2019 Feb 23;20(4):972.
doi: 10.3390/ijms20040972.

Role of p90RSK in Kidney and Other Diseases

Ling Lin  1 , Samantha A White  2 , Kebin Hu  3
Affiliations
Review

Role of p90RSK in Kidney and Other Diseases

Ling Lin et al. Int J Mol Sci. .

Abstract

The 90 kDa ribosomal s6 kinases (RSKs) are a group of serine/threonine kinases consisting of 4 RSK isoforms (RSK1-4), of which RSK1 is also designated as p90RSK. p90RSK plays an important role in the Ras-mitogen-activated protein kinase (MAPK) signalling cascade and is the direct downstream effector of Ras-extracellular signal-regulated kinase (ERK1/2) signalling. ERK1/2 activation directly phosphorylates and activates p90RSK, which, in turn, activates various signalling events through selection of different phosphorylation substrates. Upregulation of p90RSK has been reported in numerous human diseases. p90RSK plays an important role in the regulation of diverse cellular processes. Thus, aberrant activation of p90RSK plays a critical role in the pathogenesis of organ dysfunction and damage. In this review, we focus on the current understanding of p90RSK functions and roles in the development and progression of kidney diseases. Roles of p90RSK, as well as other RSKs, in cardiovascular disorders and cancers are also discussed.

Keywords: atherosclerosis; kidney; kinase inhibitors; p90RSK; pathophysiology; signalling.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1
Role of the 90 kDa ribosomal s6 kinases (p90RSK), one of the downstream mediators of extracellular signal-regulated kinase (ERK) pathway, in diseases. When the receptor tyrosine kinase (RTK, green) gets activated by a ligand (purple), it stimulates the activation of the docking proteins growth factor receptor-bound protein 2 (GRB2) and son of sevenless (SOS). SOS helps remove the guanosine diphosphate (GDP) from Rat sarcoma (Ras), allowing it to bind guanosine triphosphate (GTP) and become activated. The Ras signalling cascade begins as Ras activates the Raf kinase, which phosphorylates mitogen-activated protein kinase kinase (MEK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2) and p90RSK. Then p90RSK phosphorylates various downstream substrates (blue) to mediate diverse cellular processes (purple) and contribute to numerous human diseases including kidney disease, cardiovascular disease and cancer (red).
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