ライフサイエンスコーパス: CaMKK

1 CaMKK and 14-3-3 co-immunoprecipitated from co-transfect

2 CaMKK and CaMKI form a multiprotein signaling complex wi

3 CaMKK signals via the gamma-isoform of CaMKI as shRNA to

4 increase in cellular Ca(2+) that activates a CaMKK-beta-AMPK pathway and inhibits mTORC1, which resul

5 Chelating intracellular Ca(2+) or abrogating CaMKK-beta function by gene silencing or chemical inhibi

6 val within the nucleus, Ca(2+)/CaM activates CaMKK and its substrate CaMKIV, the CREB kinase.

7 influx through the TRPC5 channels activates CaMKK and CaMKIgamma, which subsequently promote axon fo

8 r another kinase capable of activating AMPK, CaMKK beta, contributed to PIA-induced AMPK activation,

9 Moreover, adenosine effect was Ca2+ and CaMKK independent, although probably associated with ups

10 wild-type (WT) and mutant forms of CaMKI and CaMKK.

11 starvation in a Ca(2+)-sensitive manner, and CaMKK-beta appears to be important for mTORC1 inactivati

12 y other members of the CaMK cascade, such as CaMKK, CaMKI, and CaMKIV.

13 2+)/calmodulin-dependent kinase kinase-beta (CaMKK-beta).

14 2+)/calmodulin-dependent kinase kinase-beta (CaMKK-beta).

15 Blocking CaMKK, CaMKIalpha/gamma, MEK/ERK, CREB, or Wnt2 prevente

16 ormation of multiple axons, whereas blocking CaMKK or CaMKI activity with pharmacological, dominant-n

17 kolin resulted in a rapid inhibition of both CaMKK and CaMKI activity.

18 n response to depolarization are mediated by CaMKK activation of CaMKI.

19 inhibited and could not be phosphorylated by CaMKK-433 (a truncated constitutively active form of CaM

20 orm of CaMKI that was also phosphorylated by CaMKK-433.

21 ts interrelationship with phosphorylation by CaMKK, we have carried out a detailed structure-function

22 its activation by CaM and phosphorylation by CaMKK.

23 +)/CaM and becomes phosphorylated on T200 by CaMKK.

24 Cgamma2 and activation of downstream calcium-CaMKK/PYK2 signaling.

25 Furthermore, we show that CaMKIgamma, CaMKK, beta-Pix, Rac1, and TrpC1/3 channels are all requ

26 identify a new signaling complex containing CaMKK/CaMKI/betaPIX/Rac that regulates the morphogenesis

27 s effect was blocked by inhibition of either CaMKK (STO-609) or ERK (UO126).

28 (dnKinase), we identified a requirement for CaMKK acting through CaMKI in the stimulation of ERKs up

29 These data indicate an essential role for CaMKK and CaMKI to link NMDA receptor-mediated Ca2+ elev

30 lear-targeted dnCaMKIV, other substrates for CaMKK, were not inhibitory.

31 However, we find that a second homolog CaMKK(Ppk34) is specifically required to stimulate AMPKa

32 hese events were significantly attenuated in CaMKK mice.

33 two inhibitory sites (Thr108 and Ser458) in CaMKK.

34 agenesis studies identified phospho-Ser74 in CaMKK as the primary 14-3-3 binding site.

35 It directly inhibited CaMKK activity, and it also blocked dephosphorylation of

36 AK1, TOS3, and ELM1 and the mammalian kinase CaMKK, which activate the yeast kinase SNF1 and its mamm

37 K) cascade that is comprised of CaMK kinase (CaMKK) and its primary downstream substrates, CaMKI and

38 d activated by a second enzyme, CaMK kinase (CaMKK).

39 e kinase on T200 by an upstream CaMK kinase (CaMKK).

40 describe a requirement for the CaMK-kinase (CaMKK) pathway upstream of ERK in LTP induction.

41 imulates calmodulin-dependent kinase kinase (CaMKK) and CaMKI to promote formation of spines and syna

42 a role for Ca(2+)/calmodulin kinase kinase (CaMKK) and its downstream target Ca(2+)/calmodulin kinas

43 /calmodulin-dependent protein kinase kinase (CaMKK) inhibition, apyrase treatment, G(q/11) antagonism

44 calmodulin-dependent protein kinase kinase (CaMKK) inhibitor, STO-609.

45 tion by CaM-dependent protein kinase kinase (CaMKK) of the membrane-associated gamma isoform of CaMKI

46 Ca(2+)/calmodulin-dependent kinase kinase (CaMKK) shows more sequence similarity to Pak1, Tos3, and

47 by Ca2+/calmodulin-dependent kinase kinase (CaMKK), although most likely it was not dependent on LKB

48 n brain CaM-regulated protein kinase kinase (CaMKK), an enzyme key to neuronal survival, as the first

49 ition of calmodulin-dependent kinase kinase (CaMKK), but not calmodulin-dependent kinase II (CaMKII)

50 blocked by inhibition of CaM-kinase kinase (CaMKK), the upstream activator of CaMKI.

51 ly with CaM-dependent protein kinase kinase (CaMKK), which is restricted to the cytoplasm.

52 calmodulin-dependent protein kinase kinase (CaMKK).

53 /calmodulin-dependent protein kinase kinase (CaMKK).

54 horylated and activated by a protein kinase (CaMKK) that is itself subject to regulation by Ca2+/calm

55 calmodulin-dependent protein kinase kinases (CaMKKs) are upstream regulators of AMP-activated protein

56 aMKI (Thr(177/180)) phosphorylation, a known CaMKK substrate.

57 th an IC50 comparable with that of the known CaMKK isoforms, CaMKKalpha and CaMKKbeta.

58 The known AMPK kinases LKB1, CaMKK, and TAK1 are not required for the activation of A

59 We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a

60 a(2+)/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adapta

61 was not observed in NSCLC cells with mutant CaMKK beta, suggesting that CaMKK beta contributes to PI

62 9, (2) overexpression of a dominant-negative CaMKK, or (3) short hairpin-mediated knockdown of CaMKK.

63 Activation of CaMKK by BDNF requires transient receptor potential cano

64 pecies (ROS), which was a known activator of CaMKK.

65 n of S511 near the CaM recognition domain of CaMKK and demonstrated by attenuation of CaM-stimulated

66 3 (a truncated constitutively active form of CaMKK).

67 The phosphorylation and inhibition of CaMKK by PKA is likely to be involved in modulating the

68 Inhibition of CaMKK did not affect the glycolytic activation induced b

69 Furthermore, inhibition of CaMKK had a much smaller impact on HSV-1 replication tha

70 Our results indicate that inhibition of CaMKK has a negligible impact on immediate-early-protein

71 evented by (1) pharmacological inhibition of CaMKK with STO-609, (2) overexpression of a dominant-neg

72 rbachol were not suppressed by inhibition of CaMKK, indicating specificity for this "cross-talk." To

73 3-carboxylic acid (STO-609), an inhibitor of CaMKK, causes a similar change in morphology and reducti

74 Both the pharmacological inhibitor of CaMKK, STO-609, and dominant-negative CaMKI (dnCaMKI), a

75 ced AMPK activation, we used an inhibitor of CaMKK, STO-609.

76 ylation, was impaired following knockdown of CaMKK or treatment with STO-609.

77 , or (3) short hairpin-mediated knockdown of CaMKK.

78 try of nearly 1 mol of phosphate per mole of CaMKK and a K(m) value of 3 microM.

79 ection with an STO-609-insensitive mutant of CaMKK or by transfection with constitutively active CaMK

80 xpression of a STO-609-insensitive mutant of CaMKK.

81 nhibition by PKA-mediated phosphorylation of CaMKK.

82 rt an additional PKA-dependent regulation of CaMKK through its interaction with protein 14-3-3.

83 These data suggest that the role of CaMKK during the viral life cycle is, in this regard, HC

84 To assess the role of CaMKK in contraction-stimulated glucose uptake, isolated

85 We propose that sequestration of CaMKK may be the molecular mechanism by which catalytica

86 nine 308 (T308) in AKT, a known substrate of CaMKK and an upstream activator of mTOR-dependent transl

87 Suppression of CaMKK or CaMKI by pharmacological inhibitors, dominant-n

88 -talk." To identify the downstream target of CaMKK that mediated ERK activation upon depolarization,

89 tive CaMKI (dnCaMKI), a downstream target of CaMKK, blocked neuronal NMDA receptor-dependent ERK acti

90 ncement of synaptic strength that depends on CaMKK/CaMKI signaling, actin dynamics, and the pattern o

91 1, and/or CaMKK2, siRNAs, and by PI3K and/or CaMKK inhibitors.

92 Combined CaMKK2 and PDK1 knockdown or CaMKK and PI3K inhibition, respectively, produced additi

93 in cross-talk with other signaling pathways: CaMKK/CaMKI can activate the mitogen-activated protein k

94 onents demonstrated that DAPK phosphorylates CaMKK with a stoichiometry of nearly 1 mol of phosphate

95 lation at Ser-555 in a process that requires CaMKK-beta.

96 In hippocampal slices CaMKK was phosphorylated under basal conditions, and act

97 emonstrated by attenuation of CaM-stimulated CaMKK autophosphorylation after DAPK phosphorylation.

98 n developing axonal growth cones, suppressed CaMKK-mediated activation of CaMKIgamma as well as axon

99 ontrolled at the level of CaMKIV rather than CaMKK.

100 Taken together, our results suggest that CaMKK is an important factor for HCMV replication and HC

101 nal roles of CaMKIV, these data suggest that CaMKK phosphorylation of CaMKIV may occur in the cytopla

102 ells with mutant CaMKK beta, suggesting that CaMKK beta contributes to PIA-induced AMPK activation in

103 The CaMKK homolog Ssp1 is constitutively required for phosph

104 K and JNK activation that was blocked by the CaMKK inhibitor, STO-609; this inhibition of ERK activat

105 nt activation of Cdr2 kinase activity by the CaMKK Ssp1.

106 dicate that in vitro and in intact cells the CaMKK/CaMKI cascade is subject to inhibition by PKA-medi

107 and provide a new physiological role for the CaMKK-CaMKI pathway.

108 entified many protein kinases, including the CaMKK-like Ssp1 and the MARK/PAR-1 family kinase Kin1, t

109 fission yeast Schizosaccharomyces pombe, the CaMKK-like protein kinase Ssp1 promotes cell cycle progr

110 ted muscles were treated with or without the CaMKK inhibitor STO-609 and then electrically stimulated

111 These data indicate that the CaMKKs function in intact cells as AMPKKs, predicting wi

112 We conclude that binding of 14-3-3 to CaMKK stabilizes its inhibition by PKA-mediated phosphor

113 In vitro, CaMKK is also phosphorylated by CaMKI at the same sites

114 In vitro, CaMKK is phosphorylated by PKA and this is associated wi

115 Interaction of 14-3-3 with CaMKK had two regulatory consequences in vitro.

116 embryonic kidney 293 cells transfected with CaMKK and stimulated with forskolin, co-transfection wit