Target intelligence / Profile preview

Ribosomal protein S6 kinase alpha-5 (MSK1) (MSK1)

Target
MSK1
Molecular classification
Enzyme, Serine/threonine-protein kinase, Ribosomal protein S6 kinase family
01

Overview

Ribosomal protein S6 kinase alpha-5 (Rps6ka5), also known as Mitogen- and stress-activated protein kinase 1 (MSK1), is a serine/threonine kinase that acts as a downstream effector of the MAPK signaling pathways [1, 4]. It is primarily located in the nucleus where it phosphorylates transcription factors such as CREB and ATF1, as well as chromatin proteins like Histone H3 and HMGN1, thereby facilitating the transcription of immediate-early genes [2, 4]. While the query specifies Mouse Rps6ka5 pre-mRNA, therapeutic development typically targets the human protein ortholog (MSK1) to modulate inflammatory and immune responses [1, 2]. MSK1 is implicated in various pathologies, including chronic inflammation, psoriasis, and certain cancers, where it promotes the production of pro-inflammatory cytokines [2]. In the context of neuroscience, MSK1 is involved in synaptic plasticity and has been studied for its potential role in neurodegenerative and neurodevelopmental disorders [4]. Experimental inhibitors like SB-747651A are used to study its biological roles, although no MSK1-specific drugs have reached clinical approval [3]. Targeting the pre-mRNA specifically is generally a research-level approach using antisense oligonucleotides to study gene regulation or splicing in murine models [1].

Other names
Mitogen- and stress-activated protein kinase 1MSK1RSKLS6K-alpha-5Rps6ka5
02

Mechanism of action

Inhibition of kinase activity to prevent phosphorylation of downstream targets like CREB and Histone H3.

03

Biological functions

Signal transductionTranscription regulationChromatin remodelingInflammatory responseCell proliferation
04

Disease associations

InflammationCancerNeurodegenerative diseasePsoriasisCardiovascular disease
05

Safety considerations

Potential for off-target kinase inhibitionSystemic suppression of stress-responsive gene expressionImpact on neuronal plasticity and memory formation
06

Interacting drugs

SB-747651A

2 more in the full profile.

07

Biomarkers

Phospho-CREB (Ser133) levelsPhospho-Histone H3 (Ser10) levels

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