During the development and organogenesis of all multicellular organisms, cell 
fate decisions determine whether cells undergo proliferation, differentiation, 
or aging. Two independent stress kinase signaling pathways, p38-MAPK, and JNKs, 
have evolved that relay developmental and environmental cues to determine cell 
responses. Although multiple stimuli can activate these two stress kinase 
pathways, the functional interactions and molecular cross-talks between these 
common second signaling cascades are poorly elucidated. Here we report that JNK 
and p38-MAPK pathways antagonistically control cellular senescence, oncogenic 
transformation, and proliferation in primary mouse embryonic fibroblasts (MEFs). 
Similarly, genetic inactivation of the JNK pathway results in impaired 
proliferation of fetal hepatoblasts in vitro and defective adult liver 
regeneration in vivo, which is rescued by inhibition of the p38-MAPK pathway. 
Thus, the balance between the two stress-signaling pathways, MKK7-JNK and 
MKK3/6-p38-MAPK, determines cell fate and links environmental and developmental 
stress to cell cycle arrest, senescence, oncogenic transformation, and adult 
tissue regeneration.