ライフサイエンスコーパス: m-calpain

1 ly shown to be a potent inhibitor of mu- and m-calpain.

2 II&III has a predicted structure similar to m-calpain.

3 ly shown to be a potent inhibitor of mu- and m-calpain.

4 nexpected manner by directly phosphorylating m-calpain.

5 ng to the major site of in vitro cleavage by m-calpain.

6 ge of YY1 by the calcium- activated protease m-calpain.

7 ons have no effect on this membrane-anchored m-calpain.

8 s dependent on the Ca(2+)-dependent protease m-calpain.

9 ated by p38 MAPK/JNK-dependent activation of m-calpain.

10 required for the activation of the anchored m-calpain.

11 rmation through a PKA mediated inhibition of m-calpain.

12 whereas late SCOP resynthesis is mediated by m-calpain.

13 not PI(4)P(1) or PIP(3), releasing the bound m-calpain.

14 that include ubiquitously expressed mu- and m-calpains.

15 which include ubiquitously expressed mu- and m-calpains.

16 PP2A co-localizes and interacts with mu- and m-calpains.

17 ases, which include widely expressed mu- and m-calpains (1).

18 ls expressing the PKA-resistant mutant human m-calpain (25% +/- 5.5% inhibition).

19 lls overexpressing a control wild-type human m-calpain (83% +/- 3.7% inhibition) but only marginally

20 nhibit epidermal growth factor (EGF)-induced m-calpain activation and thereby EGF-induced fibroblast

21 Previously, we demonstrated that m-calpain activation by growth factors requires extracel

22 conclusion, we describe a novel mechanism of m-calpain activation by interaction with the plasma memb

23 The failure of m-calpain activation in the absence of PIP(2) points to

24 rotective, while extrasynaptic NMDAR-coupled m-calpain activation is neurodegenerative.

25 y degrading SCOP and activating ERK, whereas m-calpain activation limits the magnitude of potentiatio

26 Interestingly, EGF-induced m-calpain activation occurs in the absence of increased

27 growth cone collapse is mediated in part by m-calpain activation, possibly through MAPK-mediated pho

28 previously have demonstrated that increased M-calpain activity downstream of epidermal growth factor

29 ated membrane localization is regulatory for m-calpain activity or merely serves as a docking site fo

30 3 ligands inhibit cell migration by blocking m-calpain activity secondary to a PKA-mediated phosphory

31 lutathione level, thioltransferase activity, m-calpain activity, and m-calpain level (as assessed by

32 and endothelial cell migration by modulating m-calpain activity.

33 eversed the IP-10 inhibition of VEGF-induced m-calpain activity.

34 ium chloride and prevented calcium-dependent m-calpain aggregation.

35 m-Calpain also co-localized with fluorescein-labeled fet

36 Treatment of CaR proteins in vitro with m-calpain also resulted in the appearance of lower molec

37 n in synaptic plasticity and may explain why m-calpain, although widely expressed in CNS, requires no

38 The concentrations of mu-, m-calpain and calpastatin detected in the extracts of bl

39 identified the calcium-dependent proteases, m-calpain and Lp82, as the primary targets of E-64 in th

40 strated that the two major calpain isozymes, m-calpain and micro-calpain, had metabolic half-lives of

41 In other studies, calpain activity and m-calpain and mu-calpain expression were measured during

42 veloped: overexpression of dominant-negative m-calpain and overexpression of calpastatin inhibitory d

43 regulate axonal growth through activation of m-calpain and p53 truncation.

44 (calpain 1 for mu-calpain and calpain 2 for m-calpain) and a common regulatory subunit (calpain 4).

45 lcium-activated neutral protease calpain II (m-calpain) and the 26 S proteasome.

46 fragments of the CaR as well as caveolin-1, m-calpain, and alkaline phosphatase were localized in me

47 increased gene expression of micro-calpain, m-calpain, and p94 and in Z-band disintegration in the e

48 The activation of m-calpain appears to be modulated by membrane interactio

49 how that the inactive heterodimeric forms of m-calpain are concentrated in caveolin-rich membrane fra

50 hat the regulatory and catalytic subunits of m-calpain are enriched in GC nuclei, including GCs grown

51 Both mu-calpains and m-calpains are heterodimers consisting of a large cataly

52 The mu- and m-calpains are major members of the calpain family that

53 This study establishes nuclear m-calpain as a regulator of CaMKIV and associated signal

54 A as a potential extracellular regulator of m-calpain at nascent sites of plasma membrane wounding.

55 ged L6 myotubes demonstrated accumulation of m-calpain at the wound site in association with the memb

56 sts expressing the EGF receptor demonstrated m-calpain being complexed with the substratum-adherent m

57 These data support a model of m-calpain binding to PIP(2) concurrent with and likely t

58 hosphorylation mimic glutamic acid-increased m-calpain binding to the membrane, consistent with block

59 Knockdown of m-calpain blocked TRPM7-induced cell rounding and cell d

60 PKA phosphorylation of m-calpain blocks the binding of the protease to PIP(2).

61 at ERK directly phosphorylates and activates m-calpain both in vitro and in vivo.

62 BDNF stimulated m-calpain but not mu-calpain serine phosphorylation, an

63 al cells with VEGF induced the activation of m-calpain, but costimulation with IP-10 significantly de

64 The phosphorylation of m-calpain by ERK and PKA by growth factors and chemokine

65 whether these growth factors could activate m-calpain by MAPK-dependent phosphorylation using cultur

66 cultured neurons, both BDNF and EGF activate m-calpain by MAPK-mediated phosphorylation.

67 hannel TRPM7 regulates cell adhesion through m-calpain by mediating the local influx of calcium into

68 sked in the holoenzyme as both activation of m-calpain by phosphorylation at serine 50 and expression

69 depletion of mu-calpain (calpain 1) but not M-calpain (calpain 2) blocked IP-9-induced calpain activ

70 Growth factors activate m-calpain (calpain 2, CAPN2) via ERK/mitogen-activated p

71 mu- and m-calpain (calpain I and calpain II) are major members o

72 t selective culture conditions, but DIIIs of m-calpain, calpain-3, and calpain-5 also interacted unde

73 ar calcium concentrations for activation and m-calpain (calpain2) needing millimolar concentrations.

74 Activities of m-calpain, calpastatin, cathepsin B, cathepsin L, and gl

75 These data provide evidence that m-calpain can be activated through the ERK cascade via d

76 t was, providing proof of the principle that m-calpain can be directly phosphorylated by PKA at this

77 cific inhibitors were used to show that only m-calpain cleaved SelK in macrophages.

78 m-Calpain colocalized with phosphoinositide biphosphate

79 m-Calpain degraded both purified CCT and CCT in cellular

80 and cytoplasmic gamma-actin, indicating that m-calpain does not cause wholesale proteolysis of other

81 of Ca2+, both of which are predicted to keep m-calpain domains IIa and IIb apart.

82 d fibroblast motility requires activation of M-calpain downstream of ERK/MAP kinase signaling.

83 Specific knock-down of mu- and/or m-calpain expression by RNA interference blocked NNK-sti

84 re, NNK promotes secretion of active mu- and m-calpain from lung cancer cells through vesicles, which

85 on results in decreased secretion of mu- and m-calpains from lung cancer cells into culture medium, w

86 cotine potently induces secretion of mu- and m-calpains from lung cancer cells into culture medium, w

87 but normal activity for the separate mu- and m-calpain gene products.

88 d restrict domain movement and help "freeze" m-calpain in an inactive state.

89 othesized that PKA might negatively modulate m-calpain in an unexpected manner by directly phosphoryl

90 tracellular calcium, there is a reduction in m-calpain in association with an increase in CaR protein

91 ntly induces phosphorylation of both mu- and m-calpain in association with their activation and incre

92 e report the 3.0 A structure of Ca(2+)-bound m-calpain in complex with the first calpastatin repeat,

93 activated by NNK, co-localized with mu- and m-calpain in cytoplasm, and directly phosphorylated mu-

94 at lenses, suggesting specific activation of m-calpain in diabetes.

95 the EGF- and VEGF-induced redistribution of m-calpain in human fibroblasts and endothelial cells.

96 ng the cellular distribution and function of m-calpain in parathyroid cells.

97 dy, we report that the activation of mu- and m-calpain in patients with type 2 diabetes has profound

98 fibroblasts to represent about 30% of total m-calpain in these cells.

99 degradation by the Ca(2+)-dependent protease m-calpain in undifferentiated but not in differentiated

100 tes closer to the C terminus not produced by m-calpain in vitro.

101 toplasm, and directly phosphorylated mu- and m-calpain in vitro.

102 ctive PP2A directly dephosphorylates mu- and m-calpains in vitro.

103 fied PKCiota directly phosphorylates mu- and m-calpains in vitro.

104 in increased phosphorylation of both mu- and m-calpains in vivo.

105 stabilized proteolytic activity of purified m-calpain incubated in the presence of mm calcium chlori

106 t epidermal growth factor (EGF) can activate m-calpain independently of calcium via mitogen-activated

107 Specific inhibition of mu-calpain, but not m-calpain, induced neutrophil polarization and chemokine

108 Furthermore, m-calpain inhibition reduced while mu-calpain knockout e

109 Addition of catalytically active m-calpain into broken cells was sufficient to produce li

110 m-calpain is a calcium-dependent heterodimeric protease

111 m-Calpain is a protease implicated in the control of cel

112 We thus hypothesized that m-calpain is activated by epidermal growth factor (EGF)

113 How m-calpain is activated in cells has challenged investiga

114 Concurrently, activated m-calpain is localized to its inner membrane milieu by b

115 indicating that TRPM7-mediated activation of m-calpain is not dependent on the nature of the divalent

116 eous cleavage pattern observed suggests that m-calpain is not the sole enzyme involved in MIP C-termi

117 The proenzyme of calpain 2 (m-calpain) is a heterodimeric calcium-dependent cysteine

118 on of the growth factor-activated calpain-2 (m-calpain) isoform also reduced transmigration and cell

119 ephosphorylates but also inactivates mu- and m-calpains, leading to suppression of migration and inva

120 ransferase activity, m-calpain activity, and m-calpain level (as assessed by Western blot) were all s

121 In mdx mice, increased m-calpain levels in dystrophic soleus muscle are associa

122 ration and invasion, suggesting that mu- and m-calpain may act as required targets in a NNK-induced m

123 of the enzyme in an inactive state and that m-calpain may also contribute to the regulation of CaR l

124 Here, we report that m-calpain may be responsible for cleaving procaspase-12,

125 naptic NMDAR-mediated neuroprotection, while m-calpain-mediated STEP degradation was associated with

126 g characteristics: (i) Ki values for mu- and m-calpains of 0.21 microM and 0.37 microM, respectively,

127 veolar fractions, we analyzed the effects of m-calpain on the CaR.

128 ecombinant p21cip1 was incubated with either m-calpain or mu-calpain, which resulted in rapid proteol

129 e proteolysis of p21cip1 catalyzed by either m-calpain or mu-calpain.

130 calcium for half-maximal activation, and the m-calpain, or calpain II, which functions at millimolar

131 extracellular signal-regulated kinase to the M-calpain pathway.

132 nd growth cone collapse were associated with m-calpain phosphorylation and prevented by inhibition of

133 m-Calpain plays a critical role in cell migration enabli

134 egradation (serum withdrawal), inhibition of m-calpain reduced protein degradation by 30%, whereas ca

135 n since the molecular basis of physiological m-calpain regulation is unknown.

136 However, mu/m-calpain remained relatively stable in both samples.

137 8 h and 24 h, respectively while activity of m-calpain remained stable.

138 PKA) phosphorylation-dependent inhibition of m-calpain, required for induced cell motility, in fibrob

139 In a prostate cancer cDNA microarray, m-calpain RNA levels were found to be significantly incr

140 Growth factor receptors activate m-calpain secondary to phosphorylation on serine 50 by E

141 Using mu-calpain- and m-calpain-selective inhibitors and mu-calpain and m-calp

142 pain-selective inhibitors and mu-calpain and m-calpain siRNAs, we found that mu-calpain-dependent PHL

143 prevented by calpain inhibition with either m-calpain-specific siRNA or inhibitors.

144 e-to-cytosol redistribution of the catalytic m-calpain subunit into the IkappaBalpha compartment.

145 rate homology with regions of calmodulin and M-calpain, suggesting that BCCIP may also bind Ca.

146 Casein has K(m) values for micro- and m-calpain that are similar to those of other substrates

147 ting growth factor-induced relocalization of m-calpain to the plasma membrane of the cells.

148 n, as the farnesylation-induced anchorage of m-calpain triggers a strong activation of this protease,

149 ntly induces phosphorylation of both mu- and m-calpains via activation of protein kinase Ciota (PKCio

150 MIP cleavage by m-calpain was carried out by incubation with purified en

151 Importantly, we found that m-calpain was enriched toward the rear of locomoting cel

152 A mutant human large subunit of m-calpain was genetically engineered to negate a putativ

153 contrast, immunostaining for the ubiquitous m-calpain was highest in the epithelium and bow region,

154 ble of cleaving immunoprecipitated SelK, but m-calpain was the predominant isoform expressed in mouse

155 alpain expression in which it was found that m-calpain was up-regulated in localized prostate cancer,

156 ctrinolysis and that mu-calpain, rather than m-calpain, was activated during RANKL-supported osteocla

157 Casein zymography and Western blot of m-calpain were performed using the water soluble fractio

158 alizes to peripheral adhesion complexes with m-calpain, where it regulates cell adhesion by controlli

159 igen up-regulates phosphorylation of mu- and m-calpains whereas C2-ceramide, a potent PP2A activator,

160 ility to replace Ca(II) in the activation of m-calpain, which in turn activates caspase-12 and degrad

161 Both mu-calpain and m-calpain, which promote the formation and disassembly o

162 cotine-stimulated phosphorylation of mu- and m-calpains, which is associated with inhibition of calpa

163 1 and Tmod4, as novel proteolytic targets of m-calpain, with Tmod1 exhibiting approximately 10-fold g

164 Our data suggest that localization of m-calpain within caveolae may contribute to maintenance

165 RPM7-induced cell rounding and activation of m-calpain, without affecting the phosphorylation state o