C-Jun N-terminal kinases
From Wikipedia, the free encyclopedia
Identifiers | |
Symbol | MAPK8 |
Alt. Symbols | PRKM8 |
Entrez | 5599 |
HUGO | 6881 |
OMIM | 601158 |
RefSeq | NM_002750 |
UniProt | P45983 |
Other data | |
Locus | Chr. 10 q11.2 |
Identifiers | |
Symbol | MAPK9 |
Alt. Symbols | PRKM9 |
Entrez | 5601 |
HUGO | 6886 |
OMIM | 602896 |
RefSeq | NM_002752 |
UniProt | P45984 |
Other data | |
Locus | Chr. 5 q35 |
mitogen-activated protein kinase 10
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Identifiers | |
Symbol | MAPK10 |
Alt. Symbols | PRKM10 |
Entrez | 5602 |
HUGO | 6872 |
OMIM | 602897 |
RefSeq | NM_002753 |
UniProt | P53779 |
Other data | |
Locus | Chr. 4 q22-q23 |
C-Jun N-terminal kinases (JNKs), originally identified as kinases that bind and phosphosphorylate c-Jun on Ser63 and Ser73 within its transcriptional activation domain, are mitogen-activated protein kinases which are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in T cell differentiation and apoptosis.
Contents |
[edit] Isoforms
The c-Jun N-terminal kinases consist of ten isoforms deriving from the three genes JNK1, JNK2 and JNK3[1]:
- JNK1 and JNK2 are ubiquitously distributed.
- By contrast, JNK3 is found mainly in neuronal tissue and testes.
[edit] Functions
JNK1 is involved in apoptosis, neurodegeneration, cell differentiation and proliferation, inflammatory conditions and cytokine production mediated by AP-1 (Activation Protein 1) such as RANTES, IL-8 and GM-CSF. [2]
Recently, JNK1 has been found to regulate Jun protein turnover by phosphorylation and activation of the ubiquitin ligase Itch.
JNKs can associate with scaffold proteins JNK Interacting Proteins as well as their upstream kinases JNKK1 and JNKK2 following their activation.
JNK, by phosphorylation, modifies the activity of numerous proteins that reside at the mitochondria or act in the nucleus. This way, JNK activity regulates several important cellular functions. Inflammatory signals, changes in levels of reactive oxygen species, Ultraviolet radiation, protein synthesis inhibitors, and a variety of stress stimuli can activate JNK. One way this activation may occur is through disruption of the conformation of sensitive protein phosphatase enzymes; specific phosphatases normally inhibit the activity of JNK itself and the activity of proteins linked to JNK activation.[3]
[edit] External links
[edit] References
- ^ Waetzig V, Herdegen T (2005). "Context-specific inhibition of JNKs: overcoming the dilemma of protection and damage". Br. J. Pharmacol 26 (9): 455–61. PMID 16054242.
- ^ Oltmanns U, Issa R, Sukkar M, John M, Chung K (2003). "Role of c-jun N-terminal kinase in the induced release of GM-CSF, RANTES and IL-8 from human airway smooth muscle cells". Br. J. Pharmacol. 139 (6): 1228–1234. doi: . PMID 12871843.
- ^ Vlahopoulos S, Zoumpourlis V, (2004). "JNK: a key modulator of intracellular signaling". Biochemistry (Mosc). 69 (8): 844–854. doi: . PMID 15377263.
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