Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.7.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3)
1_MSQSK 6_ GKKRN 11_ PGLKI 16_ PKEAF 21_ EQPQT 26_ SSTPP 31_ RDLDS 36_ KACIS 41_ IGNQN 46_ FEVKA 51_ DDLEP 56_ IMELG 61_ RGAYG 66_ VVEKM 71_ RHVPS 76_ GQIMA 81_ VKRIR 86_ ATVNS 91_ QEQKR 96_ LLMDL 101_ DISMR 106_ TVDCP 111_ FTVTF 116_ YGALF 121_ REGDV 126_ WICME 131_ LMDTS 136_ LDKFY 141_ KQVID 146_ KGQTI 151_ PEDIL 156_ GKIAV 161_ SIVKA 166_ LEHLH 171_ SKLSV 176_ IHRDV 181_ KPSNV 186_ LINAL 191_ GQVKM 196_ CDFGI 201_ SGYLV 206_ DSVAK 211_ TIDAG 216_ CKPYM 221_ APERI 226_ NPELN 231_ QKGYS 236_ VKSDI 241_ WSLGI 246_ TMIEL 251_ AILRF 256_ PYDSW 261_ GTPFQ 266_ QLKQV 271_ VEEPS 276_ PQLPA 281_ DKFSA 286_ EFVDF 291_ TSQCL 296_ KKNSK 301_ ERPTY 306_ PELMQ 311_ HPFFT 316_ LHESK 321_ GTDVA 326_SFVKL
1: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases