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the 10th letter of the Roman alphabet (同)j

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(連続するものの)10番目,第10番のもの

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/25 05:26:55」(JST)

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c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock. They also play a role in T cell differentiation and the cellular apoptosis pathway. Activation occurs through a dual phosphorylation of threonine (Thr) and tyrosine (Tyr) residues within a Thr-Pro-Tyr motif located in kinase subdomain VIII. Activation is carried out by two MAP kinases, MKK4 and MKK7 and JNK can be inactivated by Ser/Thr and Tyr protein phosphatases.^[1] It has been suggested that this signaling pathway contributes to inflammatory responses in mammals and insects.^{[citation needed]}

Isoforms

The c-Jun N-terminal kinases consist of ten isoforms derived from three genes: JNK1 (four isoforms), JNK2 (four isoforms) and JNK3 (two isoforms).^[2] Each gene is expressed as either 46 kDa or 55 kDa protein kinases, depending upon how the 3' coding region of the corresponding mRNA is processed. There have been no functional differences documented between the 46 kDa and the 55 kDa isoform, however, a second form of alternative splicing occurs within transcripts of JNK1 and JNK2, yielding JNK1-α, JNK2-α and JNK1-β and JNK2-β. Differences in interactions with protein substrates arise because of the mutually exclusive utilization of two exons within the kinase domain.^[1]

c-Jun N-terminal kinase isoforms have the following tissue distribution:

JNK1 and JNK2 are found in all cells and tissues.^[3]
JNK3 is found mainly in the brain, but is also found in the heart and the testes.^[3]

Function

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.^[4]

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. Downstream molecules that are activated by JNK include c-Jun, ATF2, ELK1, SMAD4, p53 and HSF1. The downstream molecules that are inhibited by JNK activation include NFAT4, NFATC1 and STAT3. By activating and inhibiting other small molecules in this way, JNK activity regulates several important cellular functions including cell growth, differentiation, survival and apoptosis.

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.^[5]

Recently, JNK1 has been found to regulate Jun protein turnover by phosphorylation and activation of the ubiquitin ligase Itch.

References

^ ^a ^b Ip YT, Davis RJ (April 1998). "Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development". Curr. Opin. Cell Biol. 10 (2): 205–19. doi:10.1016/S0955-0674(98)80143-9. PMID 9561845.
^ Waetzig V, Herdegen T (2005). "Context-specific inhibition of JNKs: overcoming the dilemma of protection and damage". Br. J. Pharmacol 26 (9): 455–61. doi:10.1016/j.tips.2005.07.006. PMID 16054242.
^ ^a ^b Bode AM, Dong Z (August 2007). "The Functional Contrariety of JNK". Mol. Carcinog. 46 (8): 591–8. doi:10.1002/mc.20348. PMC 2832829. PMID 17538955. 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
^ Vlahopoulos S, Zoumpourlis VC (August 2004). "JNK: a key modulator of intracellular signaling". Biochemistry Mosc. 69 (8): 844–54. doi:10.1023/B:BIRY.0000040215.02460.45. PMID 15377263.
^ Oltmanns U, Issa R, Sukkar MB, John M, Chung KF (July 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): 1228–34. doi:10.1038/sj.bjp.0705345. PMC 1573939. PMID 12871843.

External links

JNK Mitogen-Activated Protein Kinases at the US National Library of Medicine Medical Subject Headings (MeSH)
Getting a Handle on Cellular JNK (from Beaker Blog)
MAP Kinase Resource

UpToDate Contents

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English Journal

Gene expression profiling and pathway analysis identify the integrin signaling pathway to be altered by IL-1β in human pancreatic cancer cells: Role of JNK.

Verma G, Bhatia H, Datta M.SourceCSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India.
Cancer letters.Cancer Lett.2012 Jul 1;320(1):86-95. Epub 2012 Feb 4.
The pro-inflammatory cytokine, IL-1β, is a critical component of the persistent inflammatory milieu that pancreatic cancer cells frequently encounter. Although several studies report diverse mechanisms responsible for this association, yet a comprehensive global analysis of the effect of IL-1β in
PMID 22313544

Stress-activated protein kinases are involved in porcine reproductive and respiratory syndrome virus infection and modulate virus-induced cytokine production.

Lee YJ, Lee C.AbstractThe present study examined the role of the p38 MAPK and JNK pathways during PRRSV infection in immortalized porcine alveolar macrophage (PAM) cells. Infection with PRRSV was found to progressively activate p38 and JNK1/2 up to 36h postinfection and then their phosphorylation levels dramatically decreased to baseline at 48h postinfection. In contrast, UV-inactivated PRRSV failed to trigger phosphorylation of these SAPKs, indicating that the post-entry process is responsible for their activation. Independent treatment of cells with a selective p38 or JNK inhibitor markedly impaired PRRSV infection, resulting in significant reduction in synthesis of viral genomic and subgenomic RNAs, viral protein expression, and progeny virus production. Notably, cytokine production in PAM cells infected with PRRSV was shown to be altered by inhibiting these SAPKs. Altogether, our data suggest that the p38 and JNK signaling pathways play pivotal roles in PRRSV replication and may regulate immune responses during virus infection.
Virology.Virology.2012 Jun 5;427(2):80-9. Epub 2012 Mar 16.
The present study examined the role of the p38 MAPK and JNK pathways during PRRSV infection in immortalized porcine alveolar macrophage (PAM) cells. Infection with PRRSV was found to progressively activate p38 and JNK1/2 up to 36h postinfection and then their phosphorylation levels dramatically decr
PMID 22424736

Japanese Journal

1-O-Tigloyl-1-O-deacetyl-nimbolinin B Inhibits LPS-Stimulated Inflammatory Responses by Suppressing NF-κB and JNK Activation in Microglia Cells

Tao Li,Zhang Fali,Hao Lili [他]
Journal of pharmacological sciences 125(4), 364-374, 2014-08
NAID 40020164468

Kobophenol A Inhibits Sodium Nitroprusside-Induced Cardiac H9c2 Cell Death through Suppressing Activation of JNK and Preserving Mitochondrial Anti-apoptotic Bcl-2 and Mcl-1

Lee Sung Ryul,Kwak Jong Hwan,Noh Su Jin [他]
Chemical and pharmaceutical bulletin 62(7), 713-718, 2014-07
NAID 40020103681

16α,17α-Epoxypregnenolone-20-oxime Prevent LPS-Induced NO Production and iNOS Expression in BV-2 Microglial Cells by Inhibiting JNK Phosphorylation

Sun Hu-Nan,Jin Mei-Hua,Han Bing [他]
Biological & pharmaceutical bulletin 37(7), 1096-1102, 2014-07
NAID 40020103442

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★リンクテーブル★

リンク元	「c-Jun N-terminal kinase」
拡張検索	「JNKキナーゼ」「JNK mitogen-activated protein kinase」「JNK kinase」「MAPキナーゼJNK」
関連記事	「J」「JN」

「c-Jun N-terminal kinase」

mitogen-activated protein kinase 10
Identifiers
Symbol	MAPK10
Alt. symbols	JNK3, PRKM10
Entrez	5602
HUGO	6872
OMIM	602897
RefSeq	NM_002753
UniProt	P53779

mitogen-activated protein kinase 9
Identifiers
Symbol	MAPK9
Alt. symbols	JNK2, PRKM9
Entrez	5601
HUGO	6886
OMIM	602896
RefSeq	NM_002752
UniProt	P45984
Other data
Locus	Chr. 5 q35

mitogen-activated protein kinase 8
Identifiers
Symbol	MAPK8
Alt. symbols	JNK1, PRKM8
Entrez	5599
HUGO	6881
OMIM	601158
RefSeq	NM_002750
UniProt	P45983
Other data
Locus	Chr. 10 q11.2