Dual specificity mitogen-activated protein kinase kinase 4 (MAP kinase kinase 4) (MAPKK 4) (EC 2.7.12.2) (JNK-activating kinase 1) (MAPK/ERK kinase 4) (MEK 4) (SAPK/ERK kinase 1) (SEK1) (Stress-activated protein kinase kinase 1) (SAPK kinase 1) (SAPKK-1) (SAPKK1) (c-Jun N-terminal kinase kinase 1) (JNKK)
1_MAAPS 6_ PSGGG 11_ GSGGG 16_ SGSGT 21_ PGPVG 26_ SPAPG 31_ HPAVS 36_ SMQGK 41_ RKALK 46_ LNFAN 51_ PPFKS 56_ TARFT 61_ LNPNP 66_ TGVQN 71_ PHIER 76_ LRTHS 81_ IESSG 86_ KLKIS 91_ PEQHW 96_ DFTAE 101_ DLKDL 106_ GEIGR 111_ GAYGS 116_ VNKMV 121_ HKPSG 126_ QIMAV 131_ KRIRS 136_ TVDEK 141_ EQKQL 146_ LMDLD 151_ VVMRS 156_ SDCPY 161_ IVQFY 166_ GALFR 171_ EGDCW 176_ ICMEL 181_ MSTSF 186_ DKFYK 191_ YVYSV 196_ LDDVI 201_ PEEIL 206_ GKITL 211_ ATVKA 216_ LNHLK 221_ ENLKI 226_ IHRDI 231_ KPSNI 236_ LLDRS 241_ GNIKL 246_ CDFGI 251_ SGQLV 256_ DSIAK 261_ TRDAG 266_ CRPYM 271_ APERI 276_ DPSAS 281_ RQGYD 286_ VRSDV 291_ WSLGI 296_ TLYEL 301_ ATGRF 306_ PYPKW 311_ NSVFD 316_ QLTQV 321_ VKGDP 326_ PQLSN 331_ SEERE 336_ FSPSF 341_ INFVN 346_ LCLTK 351_ DESKR 356_ PKYKE 361_ LLKHP 366_ FILMY 371_ EERAV 376_ EVACY 381_ VCKIL 386_ DQMPA 391_TPSSP
1: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14