Related Experiment Video
Updated: Jul 12, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
Ribosomal S6 kinase 2 is a key regulator in tumor promoter induced cell transformation
Yong-Yeon Cho1, Ke Yao, Hong-Gyum Kim
1Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
Abstract:
The ribosomal S6 kinase 2 (RSK2), a member of the p90(RSK) (RSK) family of proteins, is a widely expressed serine/threonine kinase that is activated by extracellular signal-regulated kinase 1/2 and phosphoinositide-dependent kinase 1 in response to many growth factors and peptide hormones. Its activation signaling enhances cell survival. However, the roles of RSK2 in cell transformation have not yet been elucidated. Here, we found that RSK2 is a critical serine/threonine kinase for the regulation of cell transformation. When cells were stimulated with tumor promoters, such as epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylation of RSK was increased within 5 min. Cell proliferation was suppressed in RSK2(-/-) mouse embryonic fibroblasts (MEFs) compared with RSK2(+/+) MEFs. Moreover, RSK2(-/-) MEFs accumulated at the G(1) phase of the cell cycle under normal cell culture conditions as well as after stimulation with EGF or TPA. In the anchorage-independent cell transformation assay (soft agar), stable expression of RSK2 in JB6 cells significantly enhanced colony formation in either the presence or absence of tumor promoters. Furthermore, knockdown of RSK2 with small interfering RNA-RSK2 suppressed constitutively active Ras (Ras(G12V))-induced foci formation in NIH3T3 cells. In addition, kaempferol, an inhibitor of RSK2, suppressed EGF-induced colony formation of JB6 Cl41 cells in soft agar, which was associated with inhibition of histone H3 phosphorylation (Ser(10)). These results showed that RSK2 is a key regulator for cell transformation induced by tumor promoters such as EGF and TPA.
Insights
Ribosomal S6 kinase 2 (RSK2) is crucial for cell transformation. RSK2 activation promotes cell proliferation and colony formation, while its inhibition suppresses tumor promoter-induced cell changes.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Ribosomal S6 kinase 2 (RSK2) is a serine/threonine kinase activated by growth factors.
- RSK2 signaling enhances cell survival.
- The role of RSK2 in cell transformation remains unclear.
Purpose of the Study:
- To investigate the role of RSK2 in cell transformation.
- To determine if RSK2 is a critical regulator of tumor promoter-induced cell changes.
Main Methods:
- RSK2 knockout mouse embryonic fibroblasts (MEFs) were used.
- Anchorage-independent cell transformation assays (soft agar) were performed.
- RSK2 knockdown and inhibition studies were conducted.
Main Results:
- RSK2 deficiency suppressed cell proliferation and caused G1 cell cycle arrest.
- RSK2 expression enhanced colony formation in soft agar assays.
- RSK2 inhibition suppressed tumor promoter-induced colony formation and histone H3 phosphorylation.
Conclusions:
- RSK2 is a critical serine/threonine kinase regulating cell transformation.
- RSK2 plays a key role in mediating the effects of tumor promoters like EGF and TPA.
- Targeting RSK2 may offer a strategy for cancer prevention or treatment.
More Related Videos
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway
Abnormal Proliferation
The Ras Gene
Ras is a superfamily...
MAPK Signaling Cascades

