2r9s
From Proteopedia
Contents |
c-Jun N-terminal Kinase 3 with 3,5-Disubstituted Quinoline inhibitor
Template:ABSTRACT PUBMED 17911023
Disease
[MK10_HUMAN] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:606369]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
Function
[MK10_HUMAN] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.[1]
About this Structure
2r9s is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See Also
Reference
- Jiang R, Duckett D, Chen W, Habel J, Ling YY, LoGrasso P, Kamenecka TM. 3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6378-82. Epub 2007 Aug 26. PMID:17911023 doi:S0960-894X(07)01011-6
