c-Jun N-terminal kinases

c-Jun N-terminal kinases
mitogen-activated protein kinase 8
Symbol MAPK8
Alt. symbols JNK1, PRKM8
Entrez 5599
HUGO 6881
OMIM 601158
RefSeq NM_002750
UniProt P45983
Other data
Locus Chr. 10 q11.2
mitogen-activated protein kinase 9
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 10
Symbol MAPK10
Alt. symbols JNK3, PRKM10
Entrez 5602
HUGO 6872
OMIM 602897
RefSeq NM_002753
UniProt P53779
Other data

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.



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]


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.


  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2832829. "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" 
  4. ^ 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. 
  5. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1573939. 

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