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Ribosomal protein S6 kinase alpha-2 (RPS6KA2)
- Target
- RPS6KA2
- Molecular classification
- Protein kinase, Serine/threonine kinase, Enzyme, Member of the ribosomal S6 kinase (RSK) family
01
Overview
Ribosomal protein S6 kinase alpha-2 is a serine/threonine-protein kinase in the RSK family, acting downstream of key growth factor receptors via the ERK/MAPK signaling pathway. It contains two non-identical kinase domains for substrate phosphorylation, regulating transcriptional activity, cell growth and differentiation, survival, and stress responses. RPS6KA2 acts as a critical effector and negative regulator of ERK activity, anchoring ERK in the cytoplasm and modulating MAPK-mediated gene expression and cell fate decisions. It has implications in cancer biology, neurological function, and developmental syndromes, making it of interest for therapeutic intervention and research on signal transduction and disease mechanisms.
- Other names
- RPS6KA2RSK3KS6A2Serine/threonine-protein kinase RSK-3Ribosomal S6 protein kinase 3
02
Mechanism of action
Inhibition of kinase activity, especially phosphorylation of downstream MAPK pathway substrates. Modulation of proliferation, differentiation, and survival through altered transcription factor activation (e.g., CREB, YB1).
03
Biological functions
Signal transductionCell proliferationCell differentiationCell survivalRegulation of transcriptionControl of translationStress responseNegative regulation of ERK/MAPK signaling
04
Disease associations
Cancer (especially hematologic cancers and epithelial ovarian cancer—potential tumor suppressor role)Coffin-Lowry syndromeNeurological and psychiatric diseases (implicated in learning and memory deficits)
05
Safety considerations
Kinase inhibitors can produce off-target effects due to kinase family homology.Potential impact on cognition and memory due to involvement in neurological signaling.Possible effects on cell proliferation and differentiation can result in oncogenic or developmental toxicity.
06
Interacting drugs
Specific clinical drugs targeting RPS6KA2 directly are not well-established as of now; however, inhibitors of the MAPK/ERK pathway, which indirectly influence RSK activity, are in therapeutic use
2 more in the full profile.
07
Biomarkers
Phosphorylation status of downstream substrates (e.g., YB1, CREB)Phospho-RSK levels (indicative of MAPK pathway activity)
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