Ribosomal S6 Kinase (RSK)

Ribosomal S6 Kinase (RSK)

The 90 kDa ribosomal S6 kinase (RSK) family of proteins is a group of highly conserved Ser/Thr kinases that regulate diverse cellular processes, such as cell growth, cell motility, cell survival and cell proliferation. RSKs are downstream effectors of the Ras–extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling cascade.

An overview of RSK

The 90 kDa ribosomal S6 kinase (RSK) family are downstream effectors of the Ras/ERK signaling pathway, regulating a variety of cellular processes including cell growth, proliferation, and survival. In 1974, ribosomal protein S6 was discovered and has aroused much interest due to the temporal correlation of ribosomal protein S6 with protein synthesis. In 1985, the group of Erikson and Maller successfully identified the protein kinases responsible for ribosomal protein S6 phosphorylation, named RSKs. In recent years, a number of studies have confirmed that the protein level of RSK is significantly higher than that of normal cells and tissues in malignant tumors and tissues, and researchers have been looking for RSK inhibitors with high efficiency and low toxicity.

Major types of RSK

There are four isoforms in RSK family, termed RSK1, RSK2, RSK3, and RSK4. Structurally, the members of RSK family have a high degree of sequence homology and are 73-80% identical with each other, distinguished by their N-terminal and C-terminal sequences. Accumulating evidence has shown that RSK1 is mainly distributed in lung, kidney, and pancreas, while both RSK2 and RSK3 are predominantly found in skeletal muscle and heart. As for RSK4, the expression of RSK4 mRNA is in low abundance in human tissues.

Inhibition of RSK

The inhibitors of RSK isoforms are attractive targets for the development of new drugs due to their inhibitory effects on tumor invasion and metastasis. is a small molecular inhibitor with strong inhibition for the four isoforms. In vitro experiments demonstrated that the inhibitory effect of BI-D1870 was related to the concentration of ATP.

RSK and diseases

Previous studies have confirmed that RSKs play a crucial role in cell growth, proliferation, apoptosis and more on, promoting the development and progression of different cancers such as prostate cancer, skin cancer, and breast cancer. Therefore, RSK family members are potential anticancer targets.


1. Romeo, Y., Zhang, X., & Roux, P. P. (2012). Regulation and function of the RSK family of protein kinases.Biochemical Journal,441(2), 553-569.

2. Sulzmaier, F. J., & Ramos, J. W. (2013). RSK isoforms in cancer cell invasion and metastasis.Cancer research.

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