ライフサイエンスコーパス: MKP-2

1 l-specificity phosphatase MKP-1 but not with MKP-2.

2 ine residues in the NH(2)-terminal domain of MKP-2.

3 Therefore, we assayed levels of MKP-2, a dual specificity phosphatase whose substrates i

4 e found that upon LPS stimulation, MKP-1 and MKP-2 accumulated with different kinetics: MKP-1 level p

5 Deletion of the C terminus from MKP-1 and MKP-2 also considerably increased their stabilities.

6 While MKP-2 also modulates macrophage activation, our study su

7 MKP-2, also a dual-specific phosphatase (DUSP 4), is a p

8 explanation for the substrate preference of MKP-2 and suggest that catalytic activation of MKP-2 upo

9 that E2F-1 is a transcriptional activator of MKP-2 and that MKP-2 is an essential cell death mediator

10 PAC1, MKP-2, and MKP-1 recognize ERK and p38, ERK and JNK, and

11 evel of MAP kinase phosphatase-1 (MKP-1) and MKP-2, and the time course was correlated with the inhib

12 of the MKP-1 gene, suggesting that MKP-1 and MKP-2 are derived from the same ancestral gene.

13 Characterization of MKP-2 as a cell death mediator may lead to the developme

14 role as a docking site for ERK and p38, the MKP-2 basic motif plays a role in regulating its nuclear

15 apacity for cytokine production increased in MKP-2(-/-) BMDMs following MKP-1 knockdown.

16 additive, as both agents together increased MKP-2 by a total of six-fold.

17 residues in the C terminus of both MKP-1 and MKP-2 by the ERK pathway.

18 rely compromised the catalytic activation of MKP-2 by these kinases.

19 Moxonidine and NGF both increased levels of MKP-2 by three-fold.

20 In addition, MKP-2(-/-) CD11c(+) dendritic cells (DCs) had reduced ex

21 is impaired in MKP-2(-/-) mice compared with MKP-2(+/+) controls whereas neuronal excitability, evoke

22 pal cultures, suggesting that the effects of MKP-2 deletion were MAPK independent.

23 phosphatase 1 (PP1), and MAPK phosphatase-2 (MKP-2) during adulthood in control and neonatally CLI-tr

24 Both in vitro and in vivo, wild type MKP-2 effectively inactivated ERK2 whereas MKP-2 mutants

25 revious studies indicate that GnRH activates MKP-2 expression in gonadotropes, dependent upon activat

26 In this study, we cloned the rat MKP-2 gene and characterized its structure.

27 organization and regulatory sequences of the MKP-2 gene for further investigation of the molecular me

28 Mice lacking the MKP-2 gene had a survival advantage over wild-type mice

29 The MKP-2 gene has four exons and three introns.

30 A 1.8 kb 5' flanking region of the MKP-2 gene is sufficient to mediate transcriptional acti

31 The organization of exons of the MKP-2 gene is very similar to that of the MKP-1 gene, su

32 NAB1, resulted in increased GnRH-stimulated MKP-2 gene transcription.

33 er and can transactivate the promoter of the MKP-2 gene.

34 signals in transcriptional activation of the MKP-2 gene.

35 ple transcription start sites (TSSs) for the MKP-2 gene.

36 -dependent transcriptional activation of the MKP-2 gene.

37 MGRE (MKP-2 GnRH response element) within the MKP-2 promoter m

38 ransgenic mice where the Dusp4 gene encoding MKP-2 has been knocked out (MKP-2(-/-) mice), we show th

39 al cortex and hippocampus, (5). no change in MKP-2 in any examined region, and (6). all five measures

40 e controls, indicating an important role for MKP-2 in EAE development.

41 odification in the accumulation of MKP-1 and MKP-2 in macrophages following LPS stimulation.

42 We hypothesized a regulatory role for MKP-2 in the setting of sepsis.

43 investigation of the molecular mechanisms of MKP-2 induction by extracellular stimuli.

44 derstand the transcriptional mechanism(s) of MKP-2 induction by GnRH, we studied the activity of a 19

45 omparably strong affinities, whereas JNK and MKP-2 interacted very weakly.

46 In this report, we have examined the MKP-2 interaction with and catalytic activation by disti

47 MKP-2 is a member of the mitogen-activated protein (MAP)

48 transcriptional activator of MKP-2 and that MKP-2 is an essential cell death mediator in the E2F-1 p

49 crophage activation, our study suggests that MKP-2 is essential to the pathogenic response of EAE, an

50 MKP-2 is greatly increased following oxidative stress, a

51 P-1 level peaked at approximately 1 h, while MKP-2 levels continued to rise for at least 6 h.

52 E2F-1 acts as a transcriptional regulator of MKP-2 (MAPK phosphatase-2), a dual specificity protein p

53 expression of MHC-II and CD40 compared with MKP-2(+/+) mice.

54 The MKP-2(-/-) mice also exhibited decreased serum levels of

55 w that long-term potentiation is impaired in MKP-2(-/-) mice compared with MKP-2(+/+) controls wherea

56 Indeed, MKP-2(-/-) mice developed reduced EAE severity, associat

57 ents revealed that CD4(+) T cells from naive MKP-2(-/-) mice had decreased cell proliferation and IL-

58 ments showed that bone marrow derived DCs of MKP-2(-/-) mice had impaired capability in antigen prese

59 h these alterations in hippocampal function, MKP-2(-/-) mice show deficits in spatial reference and w

60 bone marrow-derived macrophages (BMDMs) from MKP-2(-/-) mice showed increased phosphorylation of the

61 d primary hippocampal cultures prepared from MKP-2(-/-) mice with no effect on EPSC amplitude observe

62 p4 gene encoding MKP-2 has been knocked out (MKP-2(-/-) mice), we show that long-term potentiation is

63 Here we investigated the mechanisms by which MKP-2 modulates central nervous system (CNS) inflammatio

64 Our results show that MKP-2 mRNA levels in the spinal cord and lymphoid organs

65 e MKP-2 effectively inactivated ERK2 whereas MKP-2 mutants incapable of binding to ERK/p38 did not.

66 ingly, enhanced stabilities of the MKP-1 and MKP-2 mutants were not associated with decreased ubiquit

67 Finally, we show that this E2F-1/MKP-2 pathway mediates apoptosis under oxidative stress

68 These data show that MKP-2 plays a role in regulating hippocampal function an

69 Although MKP-2 preferentially inactivates extracellular signal-re

70 that E2F-1 is physically associated with the MKP-2 promoter and can transactivate the promoter of the

71 Functional analysis of the MKP-2 promoter confirmed a requirement for the protein k

72 GRE (MKP-2 GnRH response element) within the MKP-2 promoter mediated promoter activation through the

73 onsistent with the putative role of Egr-1 in MKP-2 promoter regulation, Egr-1 protein expression clos

74 binds to a perfect palindromic motif in the MKP-2 promoter.

75 er, the inhibitory effect of thapsigargin on MKP-2 protein expression previously identified was not m

76 on closely correlated with the expression of MKP-2 protein in alpha T3-1 cells.

77 S stimulation had little effect on MKP-1 and MKP-2 protein levels, but hindered their detection by an

78 we studied the activity of a 198-nucleotide MKP-2 proximal promoter region that supports GnRH respon

79 Our studies suggest that MKP-1 and MKP-2 stability is regulated by ERK-mediated phosphoryla

80 es apoptosis under oxidative stress and that MKP-2 suppresses tumor formation in nude mice.

81 These data support a mechanism by which MKP-2 targets ERK deactivation, thereby decreasing MKP-1

82 e characterize a new MAP kinase phosphatase, MKP-2, that is induced in human peripheral blood T cells

83 two C-terminal serine residues in MKP-1 and MKP-2 to alanine decreased their half-lives, while mutat

84 ammalian genes, to MAP kinase phosphatase 2 (MKP-2), to reversion-induced LIM protein (RIL) and to cy

85 P-2 and suggest that catalytic activation of MKP-2 upon binding to its substrates is crucial for its

86 Degradation of both MKP-1 and MKP-2 was attenuated by proteasomal inhibitors.

87 We found that the catalytic activity of MKP-2 was enhanced dramatically by ERK and JNK but was a

88 Remarkably, the stability of both MKP-1 and MKP-2 was markedly decreased in macrophages in the prese

89 Moxonidine-induced induction of MKP-2 was time- and dose-dependent and could be blocked

90 Accumulation of both MKP-1 and MKP-2 were attenuated by inhibition of the ERK cascade.

91 By contrast, p38 and ERK bound MKP-2 with comparably strong affinities, whereas JNK and