About JNK2/SAPK1 / Jun N-terminal Kinase:
C-Jun N-terminal kinases (JNKs) and Serine/threonine-protein kinase SAPK1 are examples of kinases. The former is used to bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to a family of mitogen-activated protein kinases and as such are responsive to stress stimuli. Examples of stress stimuli known to have catalytic effects are heat shock, ultraviolet radiation, cytokines, and osmotic shock.
These kinases also play a role in T cell differentiation and the cellular apoptosis pathway. They are activated by a dual phosphorylation of threonine (Thr) and tyrosine (Tyr) residues within a Thr-Pro-Tyr motif located in kinase subdomain VIII. Two MAP kinases, MKK4 and MKK7 are responsible for activation, and JNK can be inactivated by Ser/Thr and Tyr protein phosphatases.
This signaling pathway has been suspected of being a contributing factor to inflammatory responses in aerobic life forms such as mammals and insects.
The c-Jun N-terminal kinases consist of ten isoforms derived from three genes. c-Jun N-terminal kinase isoforms have a clear pattern of tissue distribution with JNK1 and JNK2 are found in all cells and tissues while JNK3 is found mainly in the brain, but is also present in the heart and the testes.
Jun N-terminal Kinase Interactions
As previously stated, a variety of stress stimuli can activate JNK / SAPK pathway apoptosis. Inflammatory signals, ultraviolet radiation, changes in levels of reactive oxygen species, or protein synthesis inhibitors can lead to this process of activation.
One way in which activation may occur is through disruption of the conformation of sensitive protein phosphatase enzymes. Phosphatases may normally inhibit the activity of JNK while specific phosphatases may affect the activity of proteins which are linked to JNK activation. JNKs can have interactions with scaffold proteins and JNK interacting proteins as well as their upstream kinases JNKK1 and JNKK2 after they have been activated.
JNK, by phosphorylation, modifies the activity of a wide range of proteins residing at the mitochondria or acting within the nucleus. Downstream molecules activated by JNK may include not only c-Jun but HSF1, ATF2, ELK1, SMAD4 and p53 while downstream molecules inhibited by JNK activation include NFAT4, NFATC1 and STAT3.
JNK activity regulates a number of key cellular functions by activating and inhibiting downstream molecules in this way. Thus, the kinases are integral for cell growth and differentiation, survival and apoptosis.
The JNK/SAPK signaling pathways play a key role in DNA repair and JNK has been linked to increased longevity in insects. In Drosophila, for example, flies with mutations that augment JNK signaling tend to accumulate less oxidative damage throughout their lifespans. Thus, they are known to live dramatically longer than otherwise identical flies found in the wild.