TNFalpha is a pleiotropic cytokine that induces either cell proliferation or cell death. Inhibition of NF-kappaB activation increases susceptibility to TNFalpha-induced death, concurrent with sustained JNK activation, an important contributor to the death response. Sustained JNK activation in NF-kappaB-deficient cells was suggested to depend on reactive oxygen species (ROS), but how ROS affect ...

The cJun NH(2)-terminal kinase (JNK) signal transduction pathway has been implicated in the growth of carcinogen-induced hepatocellular carcinoma. However, the mechanism that accounts for JNK-regulated tumor growth is unclear. Here we demonstrate that compound deficiency of the two ubiquitously expressed JNK isoforms (JNK1 and JNK2) in hepatocytes does not prevent hepatocellular carcinoma devel...

Previous studies have demonstrated that gamma-irradiation (IR)-induced apoptosis in multiple myeloma (MM) is associated with activation of stress-activated protein kinase (SAPK). In the present study, we examined the molecules downstream of SAPK/C-Jun N-terminal kinase (JNK), focusing on the role of retinoblastoma protein (Rb) during IR-induced MM cell apoptosis. The results demonstrate that IR...

BACKGROUND Important signaling properties, like adaptation, oscillations, and bistability, can emerge at the level of relatively simple systems of signaling proteins. Here, we have examined the quantitative properties of one well-studied signaling system, the JNK cascade. We experimentally assessed the response of JNK to a physiological stimulus (progesterone) and a pathological stress (hyperos...

BACKGROUND During Drosophila embryogenesis, Jun kinase (JNK) signaling has been shown to play a key role in regulating the morphogenetic process of dorsal closure, which also serves as a model for epithelial sheet fusion during wound repair. During dorsal closure the JNK signaling cascade in the dorsal-most (leading edge) cells of the epidermis activates the AP-1 transcription factor comprised ...

Sphingomyelinase (SMase) and its product ceramide have recently attracted a great deal of attention because of their possible role in the signal transduction pathway. However, the role of sphingomyelinase in UV-induced c-June N-terminal kinase (JNK) activation is still unclear. Thus, we investigated this issue directly using a genetic SMase-deficient (2 approximately 3% residual acid SMase acti...

Mitogen-activated protein kinase (MAPK) cascades are involved in inflammation and tissue destruction in rheumatoid arthritis (RA). In particular, c-Jun N-terminal kinase (JNK) is highly activated in RA fibroblast-like synoviocytes and synovium. However, defining the precise function of this kinase has been difficult because a selective JNK inhibitor has not been available. We now report the use...

Arsenic trioxide induces c-jun N-terminal kinase (JNK) activation and apoptosis in acute promyelocytic leukemia (APL), where it has major clinical activity, but whether JNK is necessary to induce apoptosis is unknown. To clarify this necessity, we established 2 arsenic trioxide (As(2)O(3))-resistant subclones of the APL cell line, NB4. Both resistant lines showed little activation of JNK1 follo...

The c-Jun N-terminal kinase (JNK) is an important mediator of physiological and pathophysiological processes in the central nervous system. Importantly, JNK not only is involved in neuronal cell death, but also plays a significant role in neuronal differentiation and regeneration. For example, nerve growth factor induces JNK-dependent neuronal differentiation in several model systems. The mecha...

The role for c-Jun N-terminal Kinase (JNK) in the control of feeding and energy balance is not well understood. Here, by use of novel and highly selective JNK inhibitors, we investigated the actions of JNK in the control of feeding and body weight homeostasis. In lean mice, intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of SR-3306, a brain-penetrant and selective pan-...