RSK-B, a Novel Ribosomal S6 Kinase Family Member, Is a CREB Kinase under Dominant Control of p38α Mitogen-activated Protein Kinase (p38αMAPK)

A novel ribosomal S6 kinase (RSK) family member, RSK-B, was identified in a p38αMAPK-baited intracellular interaction screen. RSK-B presents two catalytic domains typical for the RSK family. The protein kinase C-like N-terminal and the calcium/calmodulin kinase-like C-terminal domains both contain conserved ATP-binding and activation consensus sequences. RSK-B is a p38αMAPK substrate, and activated by p38αMAPK and, more weakly, by ERK1. RSK-B phosphorylates the cAMP response element-binding protein (CREB) and c-Fos peptides. In intracellular assays, RSK-B drives cAMP response element- and AP1-dependent reporter expression. RSK-B locates to the cell nucleus and co-translocates p38αMAPK. In conclusion, RSK-B is a novel CREB kinase under dominant p38αMAPKcontrol, also phosphorylating additional substrates.