STIMULATION OF THE STRESS-ACTIVATED MITOGEN-ACTIVATED PROTEIN-KINASE SUBFAMILIES IN PERFUSED HEART - P38 RK MITOGEN-ACTIVATED PROTEIN-KINASES AND C-JUN N-TERMINAL KINASES ARE ACTIVATED BY ISCHEMIA/REPERFUSION/

It has recently been recognized that cellular stresses activate certai n members of the mitogen-activated protein kinase (MAPK) superfamily. One role of these ''stress-activated'' MAPKs is to increase the transa ctivating activity of the transcription factors c-Jun, Elk1, and ATF2. These findings may be particularly relevant to hearts that have been exposed to pathological stresses. Using the isolated perfused rat hear t, we show that global ischemia does not activate the 42- and 44-kD ex tracellular signal-regulated (protein) kinase (ERK) subfamily of MAPKs but rather stimulates a 38-kD activator of MAPK-activated protein kin ase-2 (MAPKAPK2). This activation is maintained during reperfusion. Th e molecular characteristics of this protein kinase suggest that it is a member of the p38/reaetivating kinase (RK) group of stress-activated MAPKs. In contrast, stress-activated MAPKs of the c-Jun N-terminal ki nase (JNK/SAPKs) subfamily are not activated by ischemia alone but are activated by reperfusion following ischemia. Furthermore, transfectio n of ventricular myocytes with activated protein kinases (MEKK1 and SE K1) that may be involved in the upstream activation of JNK/SAPKs induc es increases in myocyte size and transcriptional changes typical of th e hypertrophic response. We speculate that activation of multiple para llel MAPK pathways may be important in the responses of hearts to cell ular stresses.