ACTIVATION OF THE PROTEIN-KINASE P38 IN THE SPINDLE ASSEMBLY CHECKPOINT AND MITOTIC ARREST

The mitogen-activated protein kinase (MAPK) superfamily comprises clas sical MAPK (also called ERK), c-Jun amino-terminal or stress-activated protein kinase (JNK or SAPK), and p38. Although MAPK is essential for meiotic processes in Xenopus oocytes and the spindle assembly checkpo int in Xenopus egg extracts, the role of members of the MAPK superfami ly in M phase or the spindle assembly checkpoint during somatic cell c ycles has not been elucidated. The kinase p38, but not MAPK or JNK, wa s activated in mammalian cultured cells when the cells were arrested i n M phase by disruption of the spindle with nocodazole, Addition of ac tivated recombinant p38 to Xenopus cell-free extracts caused arrest of the extracts in M phase, and injection of activated p38 into cleaving embryos induced mitotic arrest. Treatment of NIH 3T3 cells with a spe cific inhibitor of p38 suppressed activation of the checkpoint by noco dazole, Thus, p38 functions as a component of the spindle assembly che ckpoint in somatic cell cycles.