The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate

被引:85
作者
Merritt, SE
Mata, M
Nihalani, D
Zhu, CX
Hu, XP
Holzman, LB
机构
[1] Univ Michigan, Sch Med, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA
[2] Dept Vet Affairs, Ann Arbor, MI 48105 USA
[3] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA
[4] Dept Vet Affairs, Pittsburgh, PA 15213 USA
关键词
D O I
10.1074/jbc.274.15.10195
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mixed lineage kinases DLK (dual leucine zipper-bearing kinase) and MLK3 have been proposed to function as mitogen-activated protein kinase kinase kinases in pathways leading to stress-activated protein kinase/c-Jun NH2-terminal kinase activation. Differences in primary protein structure place these MLK (mixed Lineage kinase) enzymes in separate subfamilies and suggest that they perform distinct functional roles. Both DLK and MLK3 associated with, phosphorylated, and activated MKK7 in vitro. Unlike MLK3, however, DLK did not phosphorylate or activate recombinant MKK4 in vitro, In confirmatory experiments performed in vivo, DLK both associated with and activated MKK7, The relative localization of endogenous DLK, MLK3, MKK4, and MKK7 was determined in cells of the nervous system. Distinct from MLK3, which was identified in non-neuronal cells, DLK and MKK7 were detected predominantly in neurons in sections of adult rat cortex by immunocytochemistry. Subcellular fractionation experiments of cerebral cortex identified DLK and MKK7 in similar nuclear and extranuclear subcellular compartments. Concordant with biochemical experiments, however, MKK4 occupied compartments distinct from that of DLK and MKK7, That DLK and MKK7 occupied subcellular compartments distinct from MKK4 was confirmed by immunocytochemistry in primary neuronal culture. The dissimilar cellular specificity of DLK and MLK3 and the specific substrate utilization and subcellular compartmentation of DLK suggest that specific mixed Lineage kinases participate in unique signal transduction events.
引用
收藏
页码:10195 / 10202
页数:8
相关论文
共 36 条
  • [1] OPTIMIZED SURVIVAL OF HIPPOCAMPAL-NEURONS IN B27-SUPPLEMENTED NEUROBASAL(TM), A NEW SERUM-FREE MEDIUM COMBINATION
    BREWER, GJ
    TORRICELLI, JR
    EVEGE, EK
    PRICE, PJ
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 1993, 35 (05) : 567 - 576
  • [2] INDUCTION OF C-FOS EXPRESSION THROUGH JNK-MEDIATED TCF/ELK-1 PHOSPHORYLATION
    CAVIGELLI, M
    DOLFI, F
    CLARET, FX
    KARIN, M
    [J]. EMBO JOURNAL, 1995, 14 (23) : 5957 - 5964
  • [3] Persistent activation of c-Jun N-terminal kinase 1 (JNK1) in gamma radiation-induced apoptosis
    Chen, YR
    Meyer, CF
    Tan, TH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (02) : 631 - 634
  • [4] IDENTIFICATION OF A NEW FAMILY OF HUMAN EPITHELIAL PROTEIN-KINASES CONTAINING 2 LEUCINE ISOLEUCINE-ZIPPER DOMAINS
    DOROW, DS
    DEVEREUX, L
    DIETZSCH, E
    DEKRETSER, T
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 213 (02): : 701 - 710
  • [5] Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6
    Enslen, H
    Raingeaud, J
    Davis, RJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (03) : 1741 - 1748
  • [6] Dual leucine zipper-bearing kinase (DLK) activates p46(SAPK) and p38(mapk) but not ERK2
    Fan, G
    Merritt, SE
    Kortenjann, M
    Shaw, PE
    Holzman, LB
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (40) : 24788 - 24793
  • [7] MEKKs, GCKs, MLKs, PAKs, TAKs, and Tpls: Upstream regulators of the c-Jun amino-terminal kinases?
    Fanger, GR
    Gerwins, P
    Widmann, C
    Jarpe, MB
    Johnson, GL
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 1997, 7 (01) : 67 - 74
  • [8] MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42
    Fanger, GR
    Johnson, NL
    Johnson, GL
    [J]. EMBO JOURNAL, 1997, 16 (16) : 4961 - 4972
  • [9] SOLUBILIZATION AND PURIFICATION OF ENZYMATICALLY ACTIVE GLUTATHIONE-S-TRANSFERASE (PGEX) FUSION PROTEINS
    FRANGIONI, JV
    NEEL, BG
    [J]. ANALYTICAL BIOCHEMISTRY, 1993, 210 (01) : 179 - 187
  • [10] IDENTIFICATION OF DISTINCT GABA(A)-RECEPTOR SUBTYPES IN CHOLINERGIC AND PARVALBUMIN-POSITIVE NEURONS OF THE RAT AND MARMOSET MEDIAL SEPTUM - DIAGONAL BAND COMPLEX
    GAO, B
    HORNUNG, JP
    FRITSCHY, JM
    [J]. NEUROSCIENCE, 1995, 65 (01) : 101 - 117