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.
Highlights
The Ras-mitogen-activated protein kinase (MAPK) pathway is an important regulator of diverse cellular processes [1,2]
The Ras-MAPK pathway is initiated by a ligand binding the receptor tyrosine kinase (RTK) receptor, followed by adaptor proteins, such as growth factor receptor-bound protein 2 (GRB2) and son of sevenless (SOS), docking onto the RTK and leading to activation of the associated Ras GTPases and recruitment of Raf
KA.dTdhiteiosenaklilny,atsheeiesoxpforremsssioanrepahtitgehrnlys ahroemsiomloilgaoruasm, wonitghRaSroKu1n-d3,7w5%ithocfotmhepsatrraubclteulreeveblesinogf RidSeKn1t-i3cadl.eAtedctdeidtiionnaadlluyl,ttthiesseuxepsrienscsliuodninpgathteeranrts, barreainsi,mluilnagr, akmidonnegy aRnSdKp1a-n3c,rweaisth[7c]o. mRSpKa4rahbales tlheevemlsoostf dRivSKer1s-e3edxpetreecstseiodninpaatdteurlnt, twisistuhepsaisntcsltuuddiinegs shheoawrt,inbgraeixnp, rleusnsgio,nkiodcncueyrrianngddpuarnincgredaesv[e7l]o. pRmSKen4thaansdtRheSKm4odset ldeitvioenrsseareexcpormesmsioonn ipnaxtt-elirnnk, ewditmhepnatastl rsetutadrideastisohnow[8i]n. g expression occurring during development and RSK4 deletions are common in xlinked mental retardation [8]
Summary
The Ras-mitogen-activated protein kinase (MAPK) pathway is an important regulator of diverse cellular processes [1,2]. The Ras-MAPK pathway is initiated by a ligand binding the receptor tyrosine kinase (RTK) receptor, followed by adaptor proteins, such as growth factor receptor-bound protein 2 (GRB2) and son of sevenless (SOS), docking onto the RTK and leading to activation of the associated Ras GTPases and recruitment of Raf. Raf activates downstream MEK1/2 and extracellular signal-regulated kinase (ERK1/2). The 90 kDa ribosomal s6 kinases (RSKs) are a group of serine/threonine kinases that play important roles in the MAPK signalling cascade and are the direct downstream effectors of ERK1/2. ERK1/2 activation directly phosphorylates and activates RSKs [3,4], which, in turn, activate various signalling events through selection of different phosphorylation substrates and modulate diverse cellular processes, such as cell proliferation, survival and motility and so forth. KA.dTdhiteiosenaklilny,atsheeiesoxpforremsssioanrepahtitgehrnlys ahroemsiomloilgaoruasm, wonitghRaSroKu1n-d3,7w5%ithocfotmhepsatrraubclteulreeveblesinogf RidSeKn1t-i3cadl.eAtedctdeidtiionnaadlluyl,ttthiesseuxepsrienscsliuodninpgathteeranrts, barreainsi,mluilnagr, akmidonnegy aRnSdKp1a-n3c,rweaisth[7c]o. mRSpKa4rahbales tlheevemlsoostf dRivSKer1s-e3edxpetreecstseiodninpaatdteurlnt, twisistuhepsaisntcsltuuddiinegs shheoawrt,inbgraeixnp, rleusnsgio,nkiodcncueyrrianngddpuarnincgredaesv[e7l]o. pRmSKen4thaansdtRheSKm4odset ldeitvioenrsseareexcpormesmsioonn ipnaxtt-elirnnk, ewditmhepnatastl rsetutadrideastisohnow[8i]n. g expression occurring during development and RSK4 deletions are common in xlinked mental retardation [8]
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