C-Jun N-terminal kinases

C-Jun N-terminal kinases

protein
Name = mitogen-activated protein kinase 8
caption =


width =
HGNCid = 6881
Symbol = MAPK8
AltSymbols = PRKM8
EntrezGene = 5599
OMIM = 601158
RefSeq = NM_002750
UniProt = P45983
PDB =
ECnumber =
Chromosome = 10
Arm = q
Band = 11.2
LocusSupplementaryData =
protein
Name = mitogen-activated protein kinase 9
caption =


width =
HGNCid = 6886
Symbol = MAPK9
AltSymbols = PRKM9
EntrezGene = 5601
OMIM = 602896
RefSeq = NM_002752
UniProt = P45984
PDB =
ECnumber =
Chromosome = 5
Arm = q
Band = 35
LocusSupplementaryData =
protein
Name = mitogen-activated protein kinase 10
caption =


width =
HGNCid = 6872
Symbol = MAPK10
AltSymbols = PRKM10
EntrezGene = 5602
OMIM = 602897
RefSeq = NM_002753
UniProt = P53779
PDB =
ECnumber =
Chromosome = 4
Arm = q
Band = 22
LocusSupplementaryData = -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.

Isoforms

The c-Jun N-terminal kinases consist of ten isoforms derived from three genes: JNK1, JNK2 and JNK3 [cite journal |author=Waetzig V, Herdegen T |title=Context-specific inhibition of JNKs: overcoming the dilemma of protection and damage |journal=Br. J. Pharmacol |volume=26 |issue=9 |pages=455–61 |year=2005 |pmid=16054242 |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16054242&query_hl=3&itool=pubmed_docsum] :
* JNK1 and JNK2 are found in all cells and tissues.cite journal
quotes =
last = Bode
first = Ann M.
authorlink =
coauthors = Zigang Dong
date =
year = 2007
month =
title = The functional contrariety of JNK
journal = Mol Carcinogen
volume = 46
issue = 8
pages = 591-8
publisher =
location =
issn =
pmid = 17538955
pmc =
doi = 10.1002/mc.20348
bibcode =
oclc =
id =
url = http://www3.interscience.wiley.com/cgi-bin/fulltext/114265450/HTMLSTART
language =
format =
accessdate = 2008-07-07
laysummary =
laysource =
laydate =
quote = "The protein products of jnk1 and jnk2 are believed to be expressed in every cell and tissue type, whereas the JNK3 protein is found primarily in brain and to a lesser extent in heart and testis."
]
* JNK3 is found mainly in the brain, but is also found in the heart and the testis.

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. [cite journal |author=Oltmanns U, Issa R, Sukkar M, John M, Chung K |title=Role of c-jun N-terminal kinase in the induced release of GM-CSF, RANTES and IL-8 from human airway smooth muscle cells |journal=Br. J. Pharmacol. |volume=139 |issue=6 |pages=1228–1234 |year=2003 |pmid=12871843 |url=http://www.nature.com/bjp/journal/v139/n6/pdf/0705345a.pdf |doi=10.1038/sj.bjp.0705345]

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. [cite journal |author=Vlahopoulos S, Zoumpourlis V, |title=JNK: a key modulator of intracellular signaling |journal=Biochemistry (Mosc). |volume=69 |issue=8 |pages=844–854 |year=2004 |pmid=15377263 |doi=10.1023/B:BIRY.0000040215.02460.45 ]

External links

*

References


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