RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under dominant control of p38α mitogen-activated protein kinase (p38α(MAPK))

Abstract

A novel ribosomal S6 kinase (RSK) family member, RSK-B, was identified in a p38α(MAPK)-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 p38α(MAPK) substrate, and activated by p38α(MAPK) 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 p38α(MAPK). In conclusion, RSK-B is a novel CREB kinase under dominant p38α(MAPK) control, also phosphorylating additional substrates.