CHARACTERIZATION OF THE STRUCTURE AND FUNCTION OF A NEW MITOGEN-ACTIVATED PROTEIN-KINASE (P38-BETA)

Mitogen-activated protein (MAP) kinase cascades represent one of the m ajor signal systems used by eukaryotic cells to transduce extracellula r signals into cellular responses, Four MAP kinase subgroups have been identified in humans: ERK, JNK (SAPK), ERK5 (BMK), and p38, Here we c haracterize a new MAP kinase, p38 beta. p38 beta is a 372-amino acid p rotein most closely related to p38. It contains a TGY dual phosphoryla tion site, which is required for its kinase activity. Like p38, p38 be ta is activated by proinflammatory cytokines and environmental stress. A comparison of events associated with the activation of p38 beta and p38 revealed differences, most notably in the preferred activation of p38 beta by MAP kinase kinase 6 (MKK6), whereas p38 was activated nea rly equally by MKK3, MKK4, and MKK6. Moreover, in. vitro and in vivo e xperiments showed a strong substrate preference by p38 beta for activa ting transcription factor 2 (ATF2), Enhancement of ATF2-dependent gene expression by p38 beta was similar to 2O-fold greater than that of p3 8 and other MAP kinases tested, The data reported here suggest that wh ile closely related, p38 beta and p38 may be regulated by differing me chanisms and may exert their actions on separate downstream targets.