ライフサイエンスコーパス: MKP-3

1 ion via the induction of MAPK phosphatase 3 (MKP-3).

2 d forkhead box O1 (FOXO1) as a substrate for MKP-3.

3 vated protein kinase phosphatase (MKP)-1 and MKP-3.

4 microM and showed selectivity for MKP-1 over MKP-3.

5 h as the dual-specificity kinase/phosphatase MKP-3.

6 ity in MCF10A cells, which had no detectable MKP-3.

7 308 cells, H-ras MCF10A cells highly express MKP-3.

8 in, resulting in the enzymatic activation of MKP-3.

9 nally coupled to the active site residues of MKP-3.

10 ivated protein kinase phosphatases CL100 and MKP-3.

11 however, blocked totally by co-expression of MKP-3.

12 MKP-3, a prototypical MKP, achieves substrate specificit

13 nesis in vivo and suggest that inhibition of MKP-3 activity may provide new therapies for T2DM.

14 MKP-3 aggregation was reversible and, 1 h after heat sho

15 in unleashes ERK activity by down-regulating MKP-3, an ERK inhibitor, and further suggest that MKP-3

16 ES cells results in the dephosphorylation of MKP-3 and activation of extracellular signal-regulated k

17 hich includes the ERK-specific enzymes DUSP6/MKP-3 and DUSP7/MKP-X.

18 Therefore, MKP-3 and MKP-1 appeared to be critical heat-labile phos

19 tively, and showed 5-10-fold selectivity for MKP-3 and MKP-1 over VH-1-related phosphatase, Cdc25B2,

20 tion of MEK1/2 and prevented inactivation of MKP-3 and MKP-1.

21 s exposed to 45 degrees C for 20 min, 90% of MKP-3 became insoluble.

22 Low level expression of MKP-3 blocks totally epidermal growth factor-stimulated

23 d inactivation of the major ERK phosphatase, MKP-3, by promoting its aggregation, so that in cells ex

24 In addition, MKP-3 can activate PEPCK promoter in synergy with dexame

25 The redistribution of MKP-3 correlated with an increased rate of ERK dephospho

26 However, unlike DUSP6/MKP-3, DUSP9/MKP-4 also inactivates the p38alpha MAP kin

27 Therefore, dysregulation of MKP-3 expression and/or function in liver may contribute

28 g a chaperone activity was unable to protect MKP-3 from heat inactivation but interfered with MEK1/2

29 We have used MKP-3-green fluorescent protein fusions in conjunction w

30 Palytoxin induced the loss of MKP-3 in a manner that corresponded to increased ERK pho

31 Conversely, shRNA knockdown of MKP-3 in both lean and obese mice resulted in decreased

32 activity and induced a corresponding loss of MKP-3 in H-ras MCF10A cells.

33 Furthermore, ectopic expression of MKP-3 in hepatoma cells by adenoviral infection increase

34 we determined how palytoxin affected ERK and MKP-3 in MCF10A human breast epithelial cells and in H-r

35 tle is known about the physiological role of MKP-3 in vivo.

36 1alpha) acted downstream of FOXO1 to mediate MKP-3-induced gluconeogenesis.

37 howed that sustained expression of exogenous MKP-3 inhibited palytoxin-stimulated ERK activation.

38 negative ERK2 mutant or a vector expressing MKP-3 inhibited the arginase II promoter activity.

39 These data indicate that MKP-3 is an important regulator of hepatic gluconeogenes

40 The amino-terminal noncatalytic domain of MKP-3 is both necessary and sufficient for nuclear expor

41 Here, we have shown that expression of MKP-3 is markedly increased in the liver of diet-induced

42 to show that the cytoplasmic localization of MKP-3 is mediated by a chromosome region maintenance-1 (

43 st to M3/6, the dual specificity phosphatase MKP-3 is selective for inactivation of ERK family MAP ki

44 We used wild-type and MKP-3 knock-out (KO) mice, a paw incision model of acute

45 l p-p38 was expressed mostly in microglia in MKP-3 KO mice, and their selective pharmacological inhib

46 if which abrogate ERK2 binding do not affect MKP-3 localization.

47 sphorylation and inactivation of MAP kinase, MKP-3 may also play a role in determining the subcellula

48 , an ERK inhibitor, and further suggest that MKP-3 may be a vulnerable target in cells that express o

49 ce the idea that regulatory proteins such as MKP-3 may play a key role in the spatio-temporal regulat

50 MKP-3-mediated dephosphorylation of FOXO1 at Ser256 prom

51 e (ERK) by the cytoplasmic phosphatase DUSP6/MKP-3 or can regulate more than one MAPK pathway as illu

52 lar basis of the cytoplasmic localization of MKP-3 or its physiological significance is unknown.

53 Consistent with this, adenovirus-mediated MKP-3 overexpression in lean mice promoted gluconeogenes

54 on was reversible and, 1 h after heat shock, MKP-3 partially resolubilized.

55 ERK) 1/2], and increased expression of DUSP6/MKP-3 phosphatase (an inhibitor of phospho-ERK1/2).

56 en together, our data strongly suggests that MKP-3 plays a role in regulating gluconeogenic gene expr

57 sistent mechanical allodynia in mice lacking MKP-3 (postoperative day 21), concurrently with persiste

58 dings strongly suggest that dysregulation of MKP-3 prevents spontaneous resolution of acute postopera

59 Recent studies show that MAPK phosphatase-3 (MKP-3) promotes gluconeogenic gene transcription in hepa

60 Transfection of an inactive ERK phosphatase (MKP-3/Pyst1) that sequesters ERK in the cytoplasm preven

61 of active mammalian MAP kinase phosphatase (MKP-3) resulted in inactivation of MAP kinase in unferti

62 Furthermore, the nuclear translocation of MKP-3 seen in the presence of leptomycin B is mediated b

63 analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 bind

64 diated by an active process, indicating that MKP-3 shuttles between the nucleus and cytoplasm.

65 Finally, we demonstrate that the ability of MKP-3 to cause the cytoplasmic retention of ERK2 require

66 ase in unfertilized eggs, as did addition of MKP-3 to lysates of unfertilized eggs.

67 of the protein also mediates the binding of MKP-3 to MAP kinase, we show that mutations of the kinas

68 ither the binding or phosphatase activity of MKP-3 toward ERK2, indicating that the kinase interactio

69 Selective regulation by M3/6 and MKP-3 was also observed upon chronic MAP kinase activati

70 In this study, we showed that MKP-3 was expressed in insulin-responsive tissues and th

71 al specificity protein kinase phosphatase 3 (MKP-3) was identified as a candidate gene that antagoniz

72 ctivated kinase (MAP) phosphatases MKP-1 and MKP-3 were elevated in neurons.

73 ogen-activated protein kinase phosphatase-3 (MKP-3), which selectively inactivates ERK.