mitogen-activated protein kinase 10 (stress-activated protein kinase JNK3, c-Jun N-terminal kinase 3, p49 3F12 MAP kinase, MAPK10, JNK3, JNK3A, PRKM10)

^[1]^[2]^[3]^[4]

Function

responds to activation by environmental stress & pro- inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 including c-Jun & ATF2 & thus regulates AP-1 transcriptional activity required for stress-induced neuronal apoptosis & the pathogenesis of glutamate excitotoxicity (putative)
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
interacts with HDAC9
activated by Thr & Tyr phosphorylation by two dual specificity kinases, MAP2K4 & MAP2K7
MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change & a large increase in Vmax
MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax inhibited by dual specificity phosphatases, such as DUSP1 inhibited by HDAC9
dually phosphorylated on Thr-221 & Tyr-223, which activates the enzyme
weakly autophosphorylated on Thr & Tyr in vitro
phosphorylates ELK-1
inhibited by map kinase phosphatase MKP-1
found in complex with beta-arrestin 2, ASK1 & MKK4

TXY motif contains the 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
mass=44070; method=Electrospray; Range=1-464^[4]

named isoforms=2, alpha-2, alpha-1

specific to a subset of neurons in the nervous system
present in the hippocampus & areas, cerebellum, striatum, brain stem, & weakly in the spinal cord
very weak expression in testis & kidney