RSK1 was the first cloned isoform of the p90 ribosomal S6 kinase family, which now contains three other members (RSK2, RSK3 and RSK4).

The genomic size of the entire RSK1 gene is about 45,260 bp and is located on the + strand of chromosome 1. This gene contains 22 coding exons.

The length of the transcript is 3,186 bp, from which the open reading frame contains 2,208 bp. While the 5UTR contains 154 bp, the 3UTR contains 824 bp.

No human pseudogene known.

The RSK1 protein consists of 735 amino acids, with an apparent molecular weight of about 85-90 kDa.

Northern analyses and RNase protection assays revealed that RSK1 is expressed in many tissues, with higher levels in skeletal muscle, kidney, lung, liver, pancreas, spleen, thymus, and brain. Although other RSK isoforms are expressed ubiquitously in the brain, RSK1 is most abundant in the cerebellum. In situ hybridization of mouse embryonic tissues revealed that RSK1 is strongly expressed in regions harbouring highly proliferating cells. These include liver, lung, and thymus, as well as olfactory, respiratory, and gut epithelia.

RSK1 is normally present in the cytoplasm, but upon mitogenic stimulation it moves into the nucleus, where it phosphorylates several substrates involved in gene transcription. Within minutes of stimulation, RSK1 was shown to accumulate transiently at the plasma membrane, where it presumably receives additional inputs necessary for activation before nuclear translocation.

Mitogenic stimulation of the Ras/ERK pathway leads to the activation of RSK1. RSK1 seems to be a multifunctional ERK effector because it participates in various cellular processes, including nuclear signalling. RSK1 was found to regulate several transcription factors, including SRF, c-Fos, and Nur77. Additional nuclear factors have been shown to be regulated by RSK1, including MITF, estrogen receptor-a nuclear factor (NF)-ATc4 and ER81. RSK1 was shown to interact with the transcriptional coactivator CREB-binding protein (CBP), which, interestingly, binds many transcription factors known to be regulated by RSK1. On the basis of the nature of its substrates, RSK1 seems to have important functions in cellular growth control and proliferation. RSK1 may stimulate cell cycle progression through the regulation of immediate early gene products, such as c-Fos, which promotes the expression of cyclin D1 during the G0/G1 transition to S phase. Other proteins through which RSK1 may stimulate proliferation include the cyclin-dependent kinase (CDK) inhibitor p27kip1, the Na+/H+ exchanger NHE-1 and the kinase GSK3. RSK1 has been shown to phosphorylate and inhibit neuronal NO synthase in response to mitogenic signaling. RSK1 may also promote proliferation by regulating cell-growth-related protein synthesis. Indeed, RSK1 was shown to phosphorylate the tumour suppressor proteins TSC2 and LKB1, thereby resulting in increased mTOR signalling and mRNA translation.

The RSK family contains four human isoforms (RSK1, RSK2, RSK3 and RSK4), which share 65-73% aa identity. RSK-related molecules have also been identified in C. elegans (T01H8.1) and D. melanogaster (RPS6-protein kinase-II), which share around 50% aa identity to human RSK1 and also contain the two kinase domains typical to RSK family members. No RSK homologues have been found in yeast or plant.

The natural variant K335T has been observed.