Rsk4

Rsk4 belongs to the p90 ribosomal S6 kinase (Rsk) family of serine/threonine protein kinases. Since its identification in 1999, Rsk4 has been the subject of very few studies and remains the least well characterized Rsk family member. The use of specific Rsk inhibitors and RNA interference should help shed light on the role and contribution of Rsk4 in cellular signaling. The gene that encodes Rsk4 is located on a locus commonly deleted in patients with X-linked mental retardation (MRX), but whether loss or mutation of Rsk4 contributes to MRX remains to be determined. While Rsk1 and Rsk2 are thought to play roles in cell survival and proliferation, Rsk4 function appears to be more enigmatic. Recent evidence suggests that Rsk4 plays an inhibitory role during embryogenesis by negatively regulating receptor tyrosine kinase (RTK) signaling. Rsk4 was also found to participate in p53-dependent growth arrest, indicating that this Rsk isoform potentially behaves as a tumor suppressor. However, aberrant expression of several X-linked genes, including Rsk4, has been observed in breast cancer. Recent evidence also indicates that Rsk4 can promote translation initiation in several human cell lines, suggesting that like other Rsk isoforms, Rsk4 may promote cancer cell growth by stimulating protein synthesis.