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mitogen-activated protein kinase 9 (c-jun NH2 terminal kinase 2, JNK2, JNK55, MAPK9, PRKM9)

Function: - responds to activation by environmental stress & pro- inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as c-Jun & ATF2 & thus regulates AP-1 transcriptional activity - in T-cells, JNK1 & JNK2 are required for polarized differentiation of T-helper cells into Th1 cells - JNK2 isoforms display different binding patterns: - alpha- 1 & alpha-2 preferentially bind to c-Jun - beta-1 & beta-2 bind to ATF2 - no correlation between binding & phosphorylation, which is achieved at about the same efficiency by all isoforms - JUNB is not a substrate for JNK2 alpha-2 - JUND binds only weakly to JNK2 alpha-2 - binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 & SPAG9/MAPK8IP4/JIP-4 - these proteins also bind other components of the JNK signaling pathway - activated by Thr & Tyr phosphorylation by either of 2 dual specificity kinases, MAP2K4 & MAP2K7 - inhibited by dual specificity phosphatases, such as DUSP1 - dually phosphorylated on Thr-183 & Tyr-185, which activates the enzyme - autophosphorylated in vitro Cofactor: Mg+2 Structure: - TXY motif contains Thr & Tyr whose phosphorylation activates the MAP kinases - belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, MAP kinase subfamily - contains 1 protein kinase domain Alternative splicing: named isoforms=4

Interactions

molecular events

Related

mitogen-activated protein kinase 9 Ag in tissue

General

c-jun NH2 terminal kinase, jun kinase (JNK) or stress-activated protein kinase (SAPK)

Properties

SIZE: entity length = 424 aa MW = 48 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 26-321 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 32-40 ATP-binding site NAME: ATP-binding site SITE: 55-55 aspartate residue {D151} TXY {183-185} Thr phosphorylation site {T183} Tyr phosphorylation site {Y185}

References

  1. Sun H, Tonks NK, Bar-Sagi D. Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1. Science. 1994 Oct 14;266(5183):285-8. PMID: 7939666
  2. Kyriakis JM, Banerjee P, Nikolakaki E, Dai T, Rubie EA, Ahmad MF, Avruch J, Woodgett JR. The stress-activated protein kinase subfamily of c-Jun kinases. Nature. 1994 May 12;369(6476):156-60. PMID: 8177321
  3. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/JNK2ID426.html
  4. UniProt :accession P45984

Databases & Figures

OMIM 602896 UniProt P45984 Pfam PF00069 Entrez Gene 5601 Kegg hsa:5601 ENZYME 2.7.11.24 MAP kinase pathways