Ma. Bogoyevitch et al., CELLULAR STRESSES DIFFERENTIALLY ACTIVATE C-JUN N-TERMINAL PROTEIN-KINASES AND EXTRACELLULAR SIGNAL-REGULATED PROTEIN-KINASES IN CULTURED VENTRICULAR MYOCYTES, The Journal of biological chemistry, 270(50), 1995, pp. 29710-29717
Anisomycin or osmotic stress induced by sorbitol activated c-Jun N-ter
minal protein kinases (JNKs) in ventricular myocytes cultured from neo
natal rat hearts. After 15-30 min, JNK was activated by 10-20-fold. Ac
tivation by anisomycin was transient, but that by sorbitol was sustain
ed for at least 4 h. In-gel JNK assays confirmed activation of two ren
aturable JNKs of 46 and 55 kDa (JNK-46 and JNK-55, respectively). An a
ntibody against human JNK1 immunoprecipitated JNK-46 activity. Endothe
lin-1, an activator of extracellular signal-regulated protein kinases
(ERKs), also transiently activated JNKs by 25-fold after 30 min. Phorb
ol 12-myristate 13-acetate did not activate the JNKs although it activ
ated ERK1 and ERK2, which phosphorylated the c-Jun transactivation dom
ain in vitro. ATP depletion and repletion achieved by incubation in cy
anide + deoxyglucose and its subsequent removal from the medium activa
ted the ERKs but failed to activate the JNKs. Sorbitol (but not anisom
ycin) also stimulated the ERKs. Sorbitol-stimulated JNK activity could
be resolved into three peaks by fast protein liquid chromatography on
a Mono Q column. The two major peaks contained JNK-46 or JNK-55. Thes
e results demonstrate that cellular stresses differentially activate t
he JNKs and ERKs and that there may be ''cross-talk'' between these MA
PK pathways.