Creation of a stress-activated p90 ribosomal S6 kinase - The carboxyl-terminal tail of the MAPK-activated protein kinases dictates the signal transduction pathway in which they function

Mitogen-activated protein kinase-activated protein kinases (MAPKAPKs) lie i mmediately downstream of the mitogen-activated protein kinases (MAPKs), ext racellular signal-regulated kinase (ERK), and p38 MAPK, Although the family of MAPKAPKs shares sequence similarity, it demonstrates selectivity for th e upstream activator. Here we demonstrate that each of the ERK- and p38 MAP K-regulated MAPKAPKs contains a MAPK docking site positioned distally to th e residue(s) phosphorylated by MAPKs. The isolated MAPK docking sites show specificity for the upstream activator similar to that reported for the ful l-length proteins. Moreover, replacement of the ERK docking site of p90 rib osomal S6 kinase with the p38 MAPK docking site of MAPKAPK2 converts p90 ri bosomal S6 kinase into a stress-activated kinase in vivo, It is apparent th at mechanisms controlling events downstream of the proline-directed MAPKs i nvolve specific MAPK docking sites within the carboxyl termini of the MAPKA PKs that determine the cascade in which the MAPKAPK functions.