ライフサイエンスコーパス: PP4

1 ement of protein phosphatase 2A (PP2A) or 4 (PP4).

2 t the levels of other phosphatases (PP2A and PP4).

3 ucture, function and potential regulation of PP4.

4 ased serine and threonine phosphorylation of PP4.

5 egulated kinase activation in the absence of PP4.

6 using okadaic acid, may in fact be those of PP4.

7 por pressures (PP1, 294 mbar; PP2, 141 mbar; PP4, 9.6 mbar; and PP9, 2.9 mbar) were examined.

8 Okadaic acid inhibits protein phosphatase 4 (PP4), a novel PP2A-related serine/threonine phosphatase,

9 uld bind and regulate protein phosphatase 4 (PP4), a tumor-promoting protein, but not the related pro

10 thern blots demonstrated the conservation of PP4 across species.

11 PP4 action is likely direct, as a portion of PP4 co-prec

12 nding of Flfl to CENP-C is required to bring PP4 activity to centromeres to maintain CENP-C and attac

13 checkpoint kinase activity, suggesting that PP4 acts directly on gamma-H2AX in cells.

14 egulating FRQ phosphorylation and stability, PP4 also dephosphorylates and activates WCC.

15 the serine/threonine protein phosphatase 4 (PP4), also called PPX.

16 sitively regulated by protein phosphatase 4 (PP4; also called PPX and PPP4), a serine/threonine phosp

17 Protein phosphatase 4 (PP4; also named PPX or PPP4) is a PP2A-related protein s

18 Taken together, our results suggest that PP4 and PP2A are two phosphatases that act at different

19 Using an in vivo RNAi screen, we identified PP4 and PP2A as phosphatases that influence Hh signaling

20 ), alpha4, but instead associates with PP2A, PP4 and PP6 catalytic subunits independently of mammalia

21 Ac is conserved in the catalytic subunits of PP4 and PP6, and PP4 is also methylated on that site, bu

22 ry protein of PP2A and the PP2A-like enzymes PP4 and PP6.

23 g subunit of the PP2Ac-related phosphatases, PP4 and PP6.

24 receptor substrate 4 (IRS-4) interacted with PP4 and that this interaction was enhanced following TNF

25 Taken together, our results show that PP4 and Wip1 are differentially required to counteract t

26 ET found in adrenals inhibited PP2A, but not PP4, and fostered 17,20 lyase activity.

27 T-1 is the major methyltransferase for PP2A, PP4, and PP6 in mouse embryonic fibroblasts (MEFs).

28 etion leads to progressive loss of all PP2A, PP4, and PP6 phosphatase complexes.

29 e family contains three enzymes called PP2A, PP4, and PP6 with separate biological functions inferred

30 e 2A (PP2A) subfamily of phosphatases, PP2A, PP4, and PP6, are multifunctional serine/threonine prote

31 pose a PPP family that includes type-2 PP2A, PP4, and PP6, each with essential functions.

32 28 coprecipitated with PP6, not with PP2A or PP4, and with SAPS domain subunits PP6R1 and PP6R3.

33 the nucleotide sequences of murine and human PP4 are distinct, their amino acid sequences are identic

34 entities of the methyltransferase enzyme for PP4 are not known.

35 induced JNK activation, our studies identify PP4 as a positive regulator for HPK1 and the HPK1-JNK si

36 Serine/threonine protein phosphatase type 4 (PP4) belongs to a family of okadaic acid and microcystin

37 Wild-type protein phosphatase 4 (PP4), but not the phosphatase-dead PP4 mutant, PP4-RL, i

38 RNAi knockdown of PP4, but not of PP2A, elevates Smo phosphorylation and a

39 We also found that PP4, but not PP2A, down-regulated IRS-4 in a phosphatase

40 ly proportional to the cellular abundance of PP4(c).

41 al product contained two major proteins: the PP4 catalytic subunit plus a protein that migrated as a

42 PP4 action is likely direct, as a portion of PP4 co-precipitates with Maf1, and purified PP4 dephosph

43 PP2A but not PP4 coimmunoprecipitated with P450c17, and suppression o

44 PP4 regulatory subunit 1 (PP4R1)-containing PP4 complex being the most dramatically affected by the

45 When the PP4 complex is silenced, repair of DNA replication-media

46 The smaller PP4 complex was purified by sequential phenyl-Sepharose,

47 ere, we establish the protein phosphatase 4 (PP4) complex as the main Maf1 phosphatase, and define th

48 Analysis of PP2A and PP4 complexes by blue native polyacrylamide gel electrop

49 e generated conventional and T-cell-specific PP4 conditional knockout mice.

50 Pulse-chase analysis revealed that PP4 decreased the half-life of IRS-4 from 4 to 1 h.

51 Anti-CD3 injection in PP4-deficient mice led to enhanced thymocyte apoptosis,

52 tion and T-cell-mediated immune responses in PP4-deficient mice were dramatically compromised.

53 PP4-deficient thymocytes showed decreased proliferation

54 reover, we found that TNF-alpha stimulated a PP4-dependent degradation of IRS-4, as indicated by the

55 PP4 dephosphorylates Kruppel-associated box domain-assoc

56 PP4 co-precipitates with Maf1, and purified PP4 dephosphorylates Maf1 in vitro.

57 ion, we showed that Thr-355 of HPK1 is a key PP4 dephosphorylation site, through which CUL7/Fbxw8 ubi

58 Despite this high homology, PP4 does not appear to associate with known PP2A regulat

59 eric localization and persistent activity of PP4 during meiotic prophase suggest a model whereby Zip1

60 PP4 efficiently dephosphorylates gamma-H2AX within monon

61 Combined with the observation that PP4 enhanced HPK1-induced JNK activation, our studies id

62 the PP4-HPK1 interaction and that wild-type PP4 enhanced, whereas a phosphatase-dead PP4 mutant inhi

63 Ptc3, as well as the protein phosphatase 4 (PP4) enzyme, Pph3.

64 NK interaction was detected, suggesting that PP4 exerts its positive regulatory effect on JNK in an i

65 PP4 existed in two complexes of approximately 270-300 an

66 in of the regulatory subunit 3 of Drosophila PP4, Falafel (Flfl), directly interacts with the centrom

67 lucidating a novel function of the conserved PP4 family phosphatase Pph3-Psy2, the yeast counterpart

68 PP4 gene deletion in the T-cell lineage resulted in aber

69 PP4 to chromosome 16, and comparison of the PP4 gene structure with that of PP2A and PP1 suggests th

70 he cloning and characterization of the human PP4 gene.

71 We also found that PP4 had phosphatase activity toward HPK1 in vivo and tha

72 P2A, another phosphatase that activates WCC, PP4 has a major function in promoting nuclear entry of W

73 Phosphoprotein phosphatase 4 (PP4) has been recently shown to participate in the regul

74 The phosphatases PP2A and PP4 have previously been shown to dephosphorylate gamma-

75 gel electrophoresis (BN-PAGE) indicates that PP4 holoenzyme complexes, like those of PP2A, are differ

76 As a first step toward characterization of PP4 holoenzymes and identification of putative PP4 regul

77 , we found that TCR stimulation enhanced the PP4-HPK1 interaction and that wild-type PP4 enhanced, wh

78 The involvement of PP4 in JNK signaling was further demonstrated by the spe

79 ltiple approaches support a central role for PP4 in Maf1 dephosphorylation, Maf1 nuclear localization

80 dization, we have examined the expression of PP4 in murine embryos and adult tissues.

81 To investigate the in vivo roles of PP4 in T cells, we generated conventional and T-cell-spe

82 activation of JNK, but not p38 and ERK2, by PP4 in transient transfection assays.

83 Pulse-chase analysis showed that PP4 increased the half-life of HPK1.

84 Moreover, we found that the PP4-induced HPK1 kinase activation was accompanied by an

85 PP2A but not PP4 inhibited 17,20 lyase activity in microsomes from cu

86 and ubiquitin-targeted degradation and that PP4 inhibited HPK1 ubiquitination.

87 ctive protein phosphatase 2A and 4 (PP2A and PP4) inhibition (IC(50) = 40-3 nM and 1.5 nM), resulting

88 the blockage of the degradation by a potent PP4 inhibitor (okadaic acid) and a phosphatase-dead PP4

89 We found that PP4 interacted with HPK1 and that the proline-rich regio

90 functions of PP4, we isolated and identified PP4-interacting proteins using a proteomic approach.

91 istically, we show that Hh downregulates Smo-PP4 interaction that is mediated by Cos2.

92 Deletion of a PP4-interaction domain (amino acids 626-678) in Smo prom

93 other PPP family phosphatases (e.g. PP2A and PP4), intercrosses with mouse lines that ubiquitously ex

94 ferent developmental stages, suggesting that PP4 is a developmentally regulated protein phosphatase.

95 Taken together, these data indicate that PP4 is a signaling component of the JNK cascade and invo

96 n the catalytic subunits of PP4 and PP6, and PP4 is also methylated on that site, but the identities

97 Thus, our results indicate that PP4 is essential for thymocyte development and pre-TCR s

98 We also found that PP4 is involved in relaying the TNF-alpha signal to c-Ju

99 We provide evidence that PP4 is involved in tumor necrosis factor (TNF)-alpha sig

100 ture with that of PP2A and PP1 suggests that PP4 is more closely related to PP2A than PP1.

101 These data indicate that one form of PP4 is similar to the core complex of PP2A in that it co

102 However, no direct PP4-JNK interaction was detected, suggesting that PP4 ex

103 We found that the ablation of PP4 led to the embryonic lethality of mice.

104 Our results define a new role for PP4-mediated dephosphorylation in the DDR, including the

105 subject to regulation by TNF-alpha and that PP4 mediates TNF-alpha-induced degradation of IRS-4.

106 ibitor (okadaic acid) and a phosphatase-dead PP4 mutant (PP4-RL).

107 ype PP4 enhanced, whereas a phosphatase-dead PP4 mutant inhibited, TCR-induced activation of HPK1 in

108 hatase 4 (PP4), but not the phosphatase-dead PP4 mutant, PP4-RL, inhibits the interaction of Fbxw8 wi

109 y the ability of PP4-RL, a dominant-negative PP4 mutant, to block TNF-alpha-induced JNK activation.

110 In pp4 mutants, early stages of crossover repair and homolo

111 ein, which also associates with phosphatases PP4 or PP6.

112 When the PP2A, PP4, or PP6 catalytic subunits were overexpressed, inhib

113 d in time-dependent activation of endogenous PP4, peaking at 10 min, as well as increased serine and

114 Here we describe a three-protein PP4 phosphatase complex in mammalian cells, containing P

115 synthetic growth effects, identified loss of PP4 phosphatase, pph3Delta and psy2Delta, as the stronge

116 in response to diverse stresses, suggesting PP4 plays a key role in the integration of cell nutritio

117 the invariant motifs of the PP1, PP2A, PP2B, PP4, PP5, and PP6 gene family.

118 unique to PP2Ac, compared with phosphatases PP4, PP6, and PP1.

119 Here we identify the phosphatase PP4 (Pph3/Psy2) as a mediator of this process in Sacchar

120 Protein phosphatase 4 (PP4, previously named protein phosphatase X (PPX)), a PP

121 AD51) or control of RPA phosphorylation (the PP4 protein phosphatase complex) are not recruited to th

122 f the mec1-100-compromised targets on HU are PP4 regulated, including a phosphoacceptor site within M

123 hrough which CUL7/Fbxw8 ubiquitin ligase and PP4 regulates HPK1 stability.

124 We further find that PP4 regulates the Hh-induced Smo cell-surface accumulati

125 differentially regulated by LCMT-1, with the PP4 regulatory subunit 1 (PP4R1)-containing PP4 complex

126 4 holoenzymes and identification of putative PP4 regulatory subunits, PP4 was purified from bovine te

127 The disruption of pp4 results in short period rhythms with low amplitude.

128 inhibited in HEK293 cells stably expressing PP4-RL in comparison to parental HEK293 cells.

129 aic acid) and a phosphatase-dead PP4 mutant (PP4-RL).

130 kinase (JNK) as indicated by the ability of PP4-RL, a dominant-negative PP4 mutant, to block TNF-alp

131 4), but not the phosphatase-dead PP4 mutant, PP4-RL, inhibits the interaction of Fbxw8 with HPK1 and

132 have analyzed the protein, cDNA and genomic PP4 sequences to provide insight into the structure, fun

133 precipitated endogenous PP6, but not PP2A or PP4, showing specificity for recognition of phosphatases

134 e X (PPX; also called protein phosphatase 4 (PP4)) that specifically associated with c-Rel, NF-kappaB

135 human/rodent somatic cell hybrid panel maps PP4 to chromosome 16, and comparison of the PP4 gene str

136 sphoprotein phosphatase 4 catalytic subunit (PP4) to be specifically required for cell cycle restart

137 s establishes a physical and functional Mec1-PP4 unit for regulating the checkpoint response.

138 PP4 was differentially expressed in murine embryos at di

139 In adult tissues, PP4 was expressed at high levels in the testis, kidney,

140 ication of putative PP4 regulatory subunits, PP4 was purified from bovine testis soluble extracts.

141 urther investigate the cellular functions of PP4, we isolated and identified PP4-interacting proteins

142 ard HPK1 in vivo and that co-transfection of PP4 with HPK1 resulted in specific kinase activation of