ライフサイエンスコーパス: CaMKI

1 CaMKI binds MARK2 within its kinase domain, but only if

2 CaMKI docks within the CCTalpha membrane-binding domain

3 CaMKI is a Ca2+/calmodulin-dependent protein kinase that

4 CaMKI is found throughout the cell cytosol, including th

5 CaMKI is required and serves as both a PINK1 and Parkin

6 CaMKI-mediated phosphorylation of Ser516 in betaPIX enha

7 CaMKI-WT was essentially inactive in the absence of CaM

8 CaMKI-WT, in the absence of CaM, or CaMKI-299 and CaMKI-

9 in gene expression are mediated by the CMK-1 CaMKI enzyme, which exhibits T(c)-dependent nucleocytopl

10 ntify a gain-of-function allele of the cmk-1 CaMKI gene in C. elegans and show that loss of the regul

11 tin 1 for access to a NES, and assembly of a CaMKI-14-3-3 zeta-CCTalpha complex is a key effector mec

12 he CaMKs and will phosphorylate and activate CaMKI, CaMKIV, and AMP-activated protein kinase.

13 r-dependent LTP induction robustly activated CaMKI, the Ca2+-stimulated Ras activator Ras-GRF1 (Ras-g

14 To understand how CaM activates CaMKI, we have characterized the activation of the enzym

15 Co-expression of constitutively active CaMKI and IV, which do not bind to alphaKAP, interfered

16 Expression of constitutively active CaMKI induced formation of multiple axons, whereas block

17 d by transfection with constitutively active CaMKI.

18 r by transfection with constitutively active CaMKI.

19 Again, CaMKI and CaMKIV were different, this time in kinetics a

20 Mutation of Ile294 and Phe298 to alanine (CaMKI-2A) resulted in measurable basal enzyme activity.

21 al mutation of Ile286 and Val290 to alanine (CaMKI-4A) increased this basal activity.

22 f the enzyme by calmodulin (CaM) also allows CaMKI to be phosphorylated and activated by a second enz

23 -WT, in the absence of CaM, or CaMKI-299 and CaMKI-298 were autoinhibited and could not be phosphoryl

24 iochemical homologues of CaMKKalpha/beta and CaMKI/IV.

25 lted in a rapid inhibition of both CaMKK and CaMKI activity.

26 CaMKK and CaMKI form a multiprotein signaling complex with the gua

27 ata indicate an essential role for CaMKK and CaMKI to link NMDA receptor-mediated Ca2+ elevation with

28 lmodulin-dependent kinase kinase (CaMKK) and CaMKI to promote formation of spines and synapses in hip

29 , we examined the potential for [Ca2+]i- and CaMKI-dependent phosphorylation of eIF4GII in vitro and

30 gulatory loop comprised of the SIK2-PP2A and CaMKI and PME-1 networks may function in fine-tuning cel

31 The functionally antagonistic SIK2-PP2A and CaMKI and PME-1 networks thus constitute a negative feed

32 indicating that activation of autoinhibited CaMKI by CaM requires a costly energetic disruption of t

33 The interaction between CaMKI and MARK2 was confirmed in vitro and in vivo by co

34 CaMKKbeta activates both CaMKI and CaMKIV when coexpressed in Jurkat T cells as j

35 rotein, and examined as a substrate for both CaMKI and CaMKIV.

36 as determined by the phosphorylation of both CaMKI and AMP-activated protein kinase (AMPK), two of Ca

37 tured rat hippocampal neurons is enhanced by CaMKI-mediated phosphorylation of Ser1156 in eukaryotic

38 In vitro, CaMKK is also phosphorylated by CaMKI at the same sites as PKA, suggesting that this reg

39 ted from HEK293T cells was phosphorylated by CaMKI, in vitro as was a recombinant fragment of eIF4GII

40 cking serine 246 cannot be phosphorylated by CaMKI/IV, a similar mutant is still phosphorylated by Ca

41 transfection with constitutively active (ca) CaMKI was blocked by dnRas.

42 context, the observed similarity between CaM.CaMKI enzyme and peptide complexes is striking, indicati

43 chain kinase are also compared with the CaM.CaMKI complexes.

44 members of the CaMK cascade, such as CaMKK, CaMKI, and CaMKIV.

45 ovide a new physiological role for the CaMKK-CaMKI pathway.

46 ify a new signaling complex containing CaMKK/CaMKI/betaPIX/Rac that regulates the morphogenesis of sp

47 t of synaptic strength that depends on CaMKK/CaMKI signaling, actin dynamics, and the pattern of syna

48 ss-talk with other signaling pathways: CaMKK/CaMKI can activate the mitogen-activated protein kinase

49 that in vitro and in intact cells the CaMKK/CaMKI cascade is subject to inhibition by PKA-mediated p

50 Here we report that inhibition of cytosolic CaMKI, but not CaMKII or nuclear CaMKIV, dramatically de

51 Overexpression of kinase-deficient CaMKI, but not CaMKII, prevented cdk4 activation, mimick

52 tion experiments revealed [Ca2+]i-dependent, CaMKI site-specific, eIF4GII phosphorylation in vivo.

53 Two distinct CaMKI/IV kinases, CaMKKalpha and CaMKKbeta, were purifie

54 by transfection with dominant-negative (dn) CaMKI but not dnCaMKIV.

55 consistent with a requirement for endogenous CaMKI for in vivo eIF4GII phosphorylation.

56 Our results establish CaMKI as a key regulator of the operating range for noci

57 Finally, CaMKI phosphorylates MARK2 on novel sites within its kin

58 increase in the CaM activation constant for CaMKI and suggests the involvement of methionine 124 in

59 aM increased the CaM activation constant for CaMKI by 10-190-fold and lowered the maximal enzyme acti

60 The kinetics of bacterially expressed human CaMKI show that the peptide syntide-2 is a relatively po

61 Ca2+/calmodulin-dependent protein kinase I (CaMKI) and the TAX-4 cyclic nucleotide-gated channel reg

62 ly activates CaM-dependent protein kinase I (CaMKI) by binding to a region in the C-terminal regulato

63 ly activates CaM-dependent protein kinase I (CaMKI) by binding to the enzyme and indirectly promotes

64 Calcium- and calmodulin-dependent kinase I (CaMKI) can regulate neurite outgrowth; however, the sign

65 tracellular infusion of active CaM-kinase I (CaMKI) into cultured hippocampal neurons enhances miniat

66 Ca2+/calmodulin-dependent protein kinase I (CaMKI) is maintained in an autoinhibited state by the in

67 Ca2+/calmodulin-dependent protein kinase I (CaMKI) is phosphorylated and activated by a protein kina

68 w that Ca(2+)/calmodulin-dependent kinase I (CaMKI) regulates thermal preferences according to past e

69 We identified a new calmodulin kinase I (CaMKI) substrate, cytidyltransferase (CCTalpha), a cruci

70 nd activates CaM-dependent protein kinase I (CaMKI) through interactions with a short sequence in its

71 a2(+)/calmodulin-dependent protein kinase I (CaMKI), an upstream kinase for phosphorylating PME-1/Ser

72 09), the upstream activator of CaM-kinase I (CaMKI), as well as by transfection with dominant-negativ

73 ownstream target Ca(2+)/calmodulin kinase I (CaMKI).

74 nt activation of Ca(2+)/calmodulin kinase-I (CaMKI), which triggers cAMP response element binding pro

75 These results identify CaMKI as a positive transducer of growth cone motility a

76 KKalpha was robustly expressed and increased CaMKI (Thr(177/180)) phosphorylation, a known CaMKK subs

77 also determined for CaM bound to the intact CaMKI enzyme.

78 ep in cyclin D/cdk4 activation that involves CaMKI and follows complex assembly, nuclear entry, and p

79 rols the actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK.

80 lmodulin-dependent protein kinases I and IV (CaMKI and CaMKIV) are closely related by primary sequenc

81 lmodulin-dependent protein kinases I and IV (CaMKI and CaMKIV, respectively) require phosphorylation

82 modulin-dependent protein kinases-I and -IV (CaMKI and CaMKIV) also induce hypertrophic responses in

83 tor of CaMKK, STO-609, and dominant-negative CaMKI (dnCaMKI), a downstream target of CaMKK, blocked n

84 osphorylation was blocked by kinase-negative CaMKI consistent with a requirement for endogenous CaMKI

85 y, inhibition of the CaMKKbeta-AMPK, but not CaMKI, signaling axis in prostate cancer cells by pharma

86 a position equivalent to that of Thr-177 of CaMKI, the activation loop site for regulation by CaM ki

87 drophobic interaction with tryptophan 303 of CaMKI.

88 The ability of CaMKI, which regulates the actin cytoskeleton, to recrui

89 hosphorylation and synergistic activation of CaMKI by an exogenous kinase.

90 mitochondrial recruitment and activation of CaMKI that precedes the colocalization of PINK1/Parkin a

91 tion of the SIK2-PP2A complex, activation of CaMKI, and downstream effects, including phosphorylation

92 rization are mediated by CaMKK activation of CaMKI.

93 dnCaMI or dnCaMKK, the upstream activator of CaMKI, exhibit collapsed morphology with a prominent red

94 CaM kinase kinase, the upstream activator of CaMKI.

95 se kinase (CaMKK), the upstream activator of CaMKI.

96 pecific amino acids in the autoinhibition of CaMKI and also in its activation by CaM and phosphorylat

97 a role for this residue in autoinhibition of CaMKI.

98 Downstream effectors of CaMKI include the MAP-kinase pathway of Ras/MEK/ERK and

99 Expression of CaMKI and MARK2 in Neuro-2A (N2a) cells and in primary h

100 7) generated a constitutively active form of CaMKI that was also phosphorylated by CaMKK-433.

101 t activation of the unphosphorylated form of CaMKI.

102 G(1), we expressed kinase-deficient forms of CaMKI and CaMKII.

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

104 CaMKK signals via the gamma-isoform of CaMKI as shRNA to CaMKIgamma, but not the other CaMKI is

105 of the membrane-associated gamma isoform of CaMKI.

106 was identified as an interacting partner of CaMKI in three independent screens.

107 ffinity complex with a 25-residue peptide of CaMKI (residues 294-318) has been determined by X-ray cr

108 ace expression as well as phosphorylation of CaMKI, AKT(T308), and mTOR.

109 re thoroughly characterize the regulation of CaMKI by CaM and its interrelationship with phosphorylat

110 important consequences in the regulation of CaMKI, CaMKIV, protein kinase B, and ERK signaling pathw

111 thermal analgesia through the regulation of CaMKI-dependent signaling.

112 corresponding to the CaM-binding sequence of CaMKI.

113 d for searching for intracellular targets of CaMKI and may have identified a new role of Ca2+ signali

114 The similarity of this motif to that of CaMKI is consistent with the 59% level of amino acid seq

115 CaMKI-WT, in the absence of CaM, or CaMKI-299 and CaMKI-298 were autoinhibited and could not

116 of multiple axons, whereas blocking CaMKK or CaMKI activity with pharmacological, dominant-negative,

117 Suppression of CaMKK or CaMKI by pharmacological inhibitors, dominant-negative (

118 KI as shRNA to CaMKIgamma, but not the other CaMKI isoforms, inhibited axon formation.

119 Mutation of Phe307 (CaMKI-F307A) resulted in increased basal enzyme activity

120 is regulated by Ca2+/CaM, and phosphorylates CaMKI and CaMKIV on Thr177 and Thr200, respectively.

121 phorylation of synapsin IIa on a distant PKA/CaMKI consensus site known to be essential for vesicle r

122 n lung cDNA expression library for potential CaMKI substrates by solid phase in situ phosphorylation

123 aMKK) and its primary downstream substrates, CaMKI and CaMKIV.

124 ((32)P) release sequencing, established that CaMKI and CaMKIV phosphorylate completely different site

125 These data support the idea that CaMKI links mitochondrial stress with the PINK1/Parkin a

126 Our results indicate that CaMKI-mediated changes in sensory gene expression contri

127 The CaMKI site, Ser(89) ((84)LLRSGSSPNL(93)), fits the expec

128 NMR spectra of CaM bound to either the CaMKI enzyme or peptide are virtually identical, indicat

129 Upon complex formation, the CaMKI peptide adopts an alpha-helical conformation, whil

130 ow that loss of the regulatory domain of the CaMKI enzyme produces thermal analgesia and shifts the o

131 We tested the hypothesis that the CaMKI-CREB-Wnt2 signaling pathway couples NDL PCB-enhanc

132 metic for interaction of calmodulin with the CaMKI enzyme.

133 ified a requirement for CaMKK acting through CaMKI in the stimulation of ERKs upon depolarization of

134 Thus CaMKI vies with CRM1/exportin 1 for access to a NES, and

135 in of CaM in regulating the access of ATP to CaMKI.

136 inase, Pnck, that is most closely related to CaMKI.

137 Mutation of Trp303 (CaMKI-W303S) resulted in a large increase in the K0.5 fo

138 t that synaptic recruitment of CP-AMPARs via CaMKI may provide a mechanistic link between NMDAR activ

139 tic architecture in response to NDL PCBs via CaMKI-CREB-Wnt2 signaling in rats.

140 ulation of cap-dependent RNA translation via CaMKI activation and selective recruitment of phosphoryl

141 Post hoc in vitro CaMKI phosphorylation assays confirm that activity promo

142 To determine whether CaMKI substrates identified by phosphorylation screening

143 ity with CaMKKalpha and 30-40% identity with CaMKI and CaMKIV themselves.

144 Interaction of MARK2 with CaMKI results in a novel, calcium-dependent pathway that

145 chiometry of the phosphorylation sites, with CaMKI preferring Ser(15) ((10)LLRTPSWGPF(19)) to Ser(85)