ライフサイエンスコーパス: NDPK

1 NDPK-A and -B have been linked to an astonishing array o

2 NDPK-A protein exhibits a half-life of approximately 6 h

3 NDPK-B directly binds and activates KCa3.1 by phosphoryl

4 NDPK-B knockout mice had unaltered NDPK-C expression but

5 NDPK-B(-/-) mice are phenotypically normal at birth with

6 NDPK-B(-/-) mice will be an essential tool with which to

7 NDPK-C is a novel critical regulator of beta-adrenocepto

8 NDPK-C was essential for the formation of an NDPK-B/G pr

9 lly inactive H118F mutant or various Ser-120 NDPK-A mutants prevented this inhibition.

10 prevented in H118F and phosphomimic Ser-120 NDPK-A mutants.

11 gh level of nucleoside diphosphate kinase A (NDPK A/nm23-H1) in neuroblastoma is associated with adva

12 report that nucleoside diphosphate kinase A (NDPK-A) interacts with both AMPK and CFTR in overlay blo

13 Nucleoside diphosphate kinase A (NDPK-A) regulates the alpha1 isoform of the AMP-activate

14 onal enzyme nucleoside diphosphate kinase A (NDPK-A) that controls cell proliferation.

15 between the nucleoside diphosphate kinase A (NDPK-A)/AMP-activated protein kinase (AMPK) alpha1 compl

16 in JB6 Cl 41-5a cells selectively abrogated NDPK-B-induced cellular transformation, implicating a po

17 whereas GCN5 depletion in cells accelerates NDPK-A degradation.

18 itching from Galphas to Galphai2 activation, NDPK-C may contribute to lower cAMP levels and the relat

19 Furthermore, we mapped the AMPK/NDPK phosphorylation site (serine 120) as a functionally

20 Cellular expression of an NDPK-A acetylation mimic or FBXO24 silencing increases N

21 NDPK-C was essential for the formation of an NDPK-B/G protein complex.

22 ylate NDPK-A directly but rather promotes an NDPK-A autophosphorylation event that involves His-118 a

23 producing a switch that may contribute to an NDPK-C-dependent cAMP reduction in HF.

24 recipitated complex consisting of NDPK A and NDPK B prepared from a neuroblastoma tumor containing th

25 he first reported linkage between NDPK-A and NDPK-B via a phosphorylation pathway and could explain t

26 r CK2alpha swaps partners between NDPK-A and NDPK-B.

27 human livers contained GAPDH aggregates and NDPK complexes.

28 with AMPK and CFTR in airway epithelia, and NDPK-A catalytic function is required for the AMPK-depen

29 We propose that GAPDH and NDPK are genetic modifiers of murine DDC-induced liver i

30 normal human skin, F(1)F(0) ATP synthase and NDPK were differentially localized, with mitochondrial e

31 f a nucleoside diphosphate protein kinase B (NDPK-B) gene in response to TPA or UV radiation (UVR).

32 e show that nucleoside diphosphate kinase B (NDPK-B), a mammalian histidine kinase, functions downstr

33 ine kinase, nucleoside diphosphate kinase B (NDPK-B), activates TRPV5 channel activity and Ca(2+) flu

34 istidine on nucleoside diphosphate kinase B (NDPK-B).

35 region, by nucleoside diphosphate kinase-B (NDPK-B).

36 wed that nucleoside diphosphate kinase beta (NDPK-B), a mammalian histidine kinase, is required for K

37 nteraction between NDPK isoforms and between NDPK isoforms and G proteins.

38 end-stage HF, the complex formation between NDPK-C and Galphai2 was increased whereas the NDPK-C/Gal

39 requirement for both the interaction between NDPK isoforms and between NDPK isoforms and G proteins.

40 This is the first reported linkage between NDPK-A and NDPK-B via a phosphorylation pathway and coul

41 ines whether CK2alpha swaps partners between NDPK-A and NDPK-B.

42 ed from the complex and translocates to bind NDPK-B, a closely related but independent isoform of NDP

43 sibly occurring at the site of activation by NDPK of a mastoparan-sensitive G-protein-dependent step

44 atine kinase, but were not phosphorylated by NDPK.

45 e analog diphosphates were phosphorylated by NDPK.

46 By dephosphorylating NDPK-B, PGAM5 negatively regulates CD4(+) T cells by inh

47 TP synthase, and nucleoside diphosphokinase (NDPK), respectively, which was supported by immunohistoc

48 ity of cytosolic nucleoside diphosphokinase (NDPK), which may provide compartmentalized GTP pools to

49 led an ecto-nucleoside diphosphokinase (ecto-NDPK) was responsible for the ADP-->ATP conversion; PCR

50 degradation was increased by inhibiting ecto-NDPK activity; confirming that the combined action of mu

51 Endogenous NDPK-B is also critical for KCa3.1 channel activity and

52 a phosphorylated intermediate essential for NDPK activity.

53 f this are largely unknown, particularly for NDPK-C.

54 ant protein may have relevance to a role for NDPK A in neuroblastoma progression.

55 The critical role for NDPK-B in the reactivation of CD4 T cells indicates that

56 Although they comprise a family of 10 genes, NDPK-A and -B are ubiquitously expressed and account for

57 The nucleoside diphosphate kinase Nm23-H4/NDPK-D forms symmetrical hexameric complexes in the mito

58 e kinase (NDPK), and knockdown of hepatocyte NDPK augmented DDC-induced ROS formation.

59 Our findings identify NDPK-C as an essential requirement for both the interact

60 and urinary Ca(2+) excretion is increased in NDPK-B(-/-) mice fed a high-Ca(2+) diet.

61 though T and B cell development is normal in NDPK-B(-/-) mice, KCa3.1 channel activity and cytokine p

62 found a serine 120-->glycine substitution in NDPK A and/or amplification of the nm23-H1 gene in advan

63 e, and we demonstrate in vivo that increased NDPK activity leads to susceptibility to energy deprivat

64 tylation mimic or FBXO24 silencing increases NDPK-A life span which, in turn, impairs cell migration

65 ally consume ATP, whereas AMPK would inhibit NDPK to conserve energy.

66 ively regulates CD4(+) T cells by inhibiting NDPK-B-mediated histidine phosphorylation and activation

67 e, protein histidine phosphatase 1, inhibits NDPK-B-activated TRPV5 in inside/out patch experiments.

68 Nucleoside-diphosphate kinase (NDPK) 2 in Arabidopsis has been identified as a phytochr

69 ated by their nucleoside diphosphate kinase (NDPK) activity.

70 orylation and nucleoside-diphosphate kinase (NDPK) characteristics but deficient phosphotransfer acti

71 ability of a nucleoside diphosphate kinase (NDPK) mutant in which the nucleophilic histidine has bee

72 mitochondrial nucleoside diphosphate kinase (NDPK) together with defects in mitochondrial transcripti

73 gy-generating nucleoside-diphosphate kinase (NDPK), and knockdown of hepatocyte NDPK augmented DDC-in

74 hotransferase nucleoside diphosphate kinase (NDPK), which maintains pools of nucleotides, as a direct

75 Nucleoside diphosphate kinases (NDPKs) are encoded by the Nme (non-metastatic cell) gene

76 Nucleoside diphosphate kinases (NDPKs) are enriched at the plasma membrane of patients w

77 knockdown of nucleoside diphosphate kinases (NDPKs) NM23-H1/H2, which produce GTP through adenosine t

78 2 (CK2), whereas H-LDH associates with local NDPK-B.

79 estingly, stable transfection of the nm23-M2/NDPK-B del-RGD or G106A mutant gene in JB6 Cl 41-5a cell

80 tudies by constitutive expression of nm23-M2/NDPK-B in TPA susceptible JB6 Cl 41-5a and TPA-resistant

81 in the nucleophile cavity of H122A, a mutant NDPK that differs from H122G by a single methyl group wi

82 uced denaturation for the recombinant mutant NDPK A and in an immunoprecipitate from a tumor containi

83 activity was lower in the recombinant mutant NDPK A and in the immunoprecipitated complex consisting

84 ually the most abundant cellular nucleotide, NDPK would normally consume ATP, whereas AMPK would inhi

85 However, the activity of NDPK, F(1)F(0) ATP synthase or the forward reaction of a

86 way and could explain the complex biology of NDPK.

87 the immunoprecipitated complex consisting of NDPK A and NDPK B prepared from a neuroblastoma tumor co

88 In vivo, depletion of NDPK-C in zebrafish embryos caused cardiac edema and ven

89 UVR significantly induced the expression of NDPK-B both in vivo hyperplastic mouse skin and in vitro

90 better understand the multiple functions of NDPK and its role in phytochrome-mediated signaling, we

91 nitively address the biological functions of NDPK-B.

92 that specific pharmacological inhibitors of NDPK-B may provide new opportunities to treat Th1- and T

93 a closely related but independent isoform of NDPK.

94 n in vivo, as short hairpin RNA knockdown of NDPK-B leads to decreased TRPV5 channel activity, and ur

95 Protein and mRNA levels of NDPK-C were upregulated in end-stage human HF, in rats a

96 Overexpression of NDPK-C in cardiomyocytes increased cAMP levels and sensi

97 ogether with the normal overall phenotype of NDPK-B(-/-) mice, suggests that specific pharmacological

98 We now report the phenotype of NDPK-B(-/-) mice.

99 whether serine/threonine phosphorylation of NDPK occurs as has been suggested by other NDPK studies,

100 ubstitution on the biochemical properties of NDPK A was investigated.

101 Here, we investigated the potential role of NDPK-C in cardiac cAMP formation and contractility.

102 alpha exclusion mutations (S120A or S122D of NDPK-A) on NDPK-A might have implications in cancer biol

103 Isoprenaline also promoted translocation of NDPK-C to the plasma membrane.

104 raction with G proteins, and localization of NDPKs.

105 sion mutations (S120A or S122D of NDPK-A) on NDPK-A might have implications in cancer biology and gen

106 the AMPK-dependent phospho-status of S122 on NDPK-A determines whether CK2alpha swaps partners betwee

107 We report that when S122 on NDPK-A is phosphorylated by AMPK alpha1 in vivo, (i.e.,

108 f NDPK occurs as has been suggested by other NDPK studies, NDPK2 putative phosphorylation site mutant

109 AMPK does not appear to phosphorylate NDPK-A directly but rather promotes an NDPK-A autophosph

110 SCF-FBXO24 polyubiquitinates NDPK-A at K85, and two NH(2)-terminal residues, L55 and

111 Recombinant NDPK A containing the Ser120-->Gly mutation exhibited re

112 K56 with Q56, an acetylation mimic, reduces NDPK-A FBXO24 binding capacity.

113 ent of AMPK upstream and directly regulating NDPK activity has widespread implications for cellular e

114 stidine protein kinase activity; significant NDPK activity was observed.

115 NM23-H4, a mitochondria-specific NDPK, colocalized with mitochondrial dynamin-like OPA1 i

116 etylation within NDPK-A, thereby stabilizing NDPK-A, whereas GCN5 depletion in cells accelerates NDPK

117 Our finding that NDPK-B is required for activation of Th1 and Th2 CD4 T c

118 -) mice and thereby support genetically that NDPK-B functions upstream of KCa3.1.

119 We previously showed that NDPK-B activates the K(+) channel KCa3.1 via histidine p

120 Taken together, these results suggest that NDPK-A exists in a functional cellular complex with AMPK

121 tously expressed and account for most of the NDPK activity.

122 We show that CK2 is part of the NDPK-A/AMPK alpha1 complex under basal (background AMPK

123 DPK-C and Galphai2 was increased whereas the NDPK-C/Galphas interaction was decreased, producing a sw

124 Thus, NDPKs interact with and provide GTP to dynamins, allowin

125 ecipitated with the mutant but not wild-type NDPK A.

126 very similar to one another and to wild-type NDPK, providing no evidence for a structurally perturbed

127 NDPK-B knockout mice had unaltered NDPK-C expression but showed contractile dysfunction and

128 of CD4 T cells indicates that understanding NDPK-B regulation should uncover novel pathways required

129 duced augmentation of contractility, whereas NDPK-C knockdown decreased cAMP levels.

130 lastoma, which suggests a mechanism by which NDPK in neuroblastoma can no longer be inhibited by AMPK

131 ling complex such that M-LDH associates with NDPK-A, AMPK alpha1 and casein kinase 2 (CK2), whereas H

132 ferase GCN5 catalyzes K56 acetylation within NDPK-A, thereby stabilizing NDPK-A, whereas GCN5 depleti

133 ed CFTR conductance with co-expression of WT NDPK-A in two-electrode voltage clamp studies, but co-ex

134 In vitro phosphorylation of WT NDPK-A was enhanced by purified active AMPK, but phospho