ライフサイエンスコーパス: MARCKS

1 MARCKS (myristoylated alanine-rich C-kinase substrate) i

2 MARCKS acted upstream of the AKT/mTOR pathway, activatin

3 MARCKS associates with membranes via the combined action

4 MARCKS expression and signaling in primary MKs is a nove

5 MARCKS inhibition by peptide significantly decreased pro

6 MARCKS is a protein kinase C (PKC) substrate that binds

7 MARCKS is an actin-binding protein that modulates vascul

8 MARCKS is known to be phosphorylated by Cdk5 in chick ne

9 MARCKS knockdown and H(2)O(2) treatment alter the archit

10 MARCKS phosphorylation has been implicated in endocytosi

11 MARCKS phosphorylation was inhibited by PKC-delta siRNA,

12 MARCKS-deficient mouse embryonic fibroblasts (MEFs) resp

13 MARCKS-ED has the added property of being a lower-molecu

14 MARCKS-like protein (MLP), recently discovered as a rege

15 ion of wild-type and PSD-mutated (S159/163A) MARCKS, we showed that elevated phospho-MARCKS promoted

16 DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP

17 S or EGFR mutations, and establishes an AKT1-MARCKS-LAMC2 feedback loop in this regulation.

18 subsequent loss of activation of GAP-43 and MARCKS, and the established role of PKCs in spinocerebel

19 oforms of PKC (PKC-betaI and PKC-alpha), and MARCKS-GFP, but only in Ca2+-containing solutions.

20 TRPC1 channels and MARCKS form signaling complexes with PI(4,5)P2 bound to

21 vel were increased with AKT1 inhibition, and MARCKS or LAMC2 knockdown abrogated migration and invasi

22 We determined that MARCKS and MARCKS-related protein specifically bind to LPS and that

23 ation and an intimate interaction of PSA and MARCKS at the cell surface was seen by confocal microsco

24 re in close contact, suggesting that PSA and MARCKS interact with each other at the plasma membrane f

25 Insertion of PSA and MARCKS-ED peptide into lipid bilayers from opposite side

26 rons confirm the interaction between PSA and MARCKS.

27 ifferences between properties of the PSD and MARCKS.

28 Both secretion and MARCKS phosphorylation were significantly enhanced by th

29 d PKC delta and enhanced mucin secretion and MARCKS phosphorylation.

30 nduced phosphorylation of PKC substrates and MARCKS.

31 its PH domain to PIP2, decreases markedly as MARCKS(151-175) sequesters most of the PIP2.

32 influence synaptic vesicle function, such as MARCKS, synapsin, and SNAP-25, were all reduced in synap

33 in segment that is responsible for attaching MARCKS reversibly to the membrane interface.

34 functional role for the interaction between MARCKS and PSA in the developing and adult nervous syste

35 ivated protein kinase, and the actin-binding MARCKS protein--was blocked by preincubation with PEG-ca

36 ly downregulates proplatelet formation; both MARCKS and Arp2 were dephosphorylated in MKs making prop

37 results suggest that phosphorylation of both MARCKS and myosin II lead to disruption of the actin cor

38 BBS-mediated NT secretion was attenuated by MARCKS siRNA.

39 s TLC-mediated activation of PKC followed by MARCKS phosphorylation and consequent detachment of MARC

40 ng properties of Gag, the well-characterized MARCKS peptide, a series of fluorescent electrostatic se

41 tosol upon PMA treatment, further confirming MARCKS activation.

42 Conversely, MARCKS silencing had little or no effect on EC migration

43 g pathway molecules (ERK, JNK, CaMKII, CREB, MARCKS, Fyn, tau).

44 s transfected with phosphorylation-deficient MARCKS, TLC failed to increase MARCKS phosphorylation or

45 We demonstrate MARCKS silencing attenuates VSMC migration and arrests V

46 by Gay et al., suggests that effector domain MARCKS peptides could play a significant role in memory

47 In contrast, the cellular protein domain MARCKS and the PS sensor Evectin2 show preference for di

48 eptide corresponding to its effector domain, MARCKS(151-175), to sequester PIP2 in model membranes co

49 , or a peptide corresponding to this domain, MARCKS(151-175), sequesters several PI(4,5)P2 and that t

50 Endogenous MARCKS and green fluorescent protein-tagged wild-type MA

51 Knockdown of endogenous MARCKS using RNAi reduced spine density and size.

52 SA or PSA-NCAM and intracellularly expressed MARCKS-GFP are in close contact, suggesting that PSA and

53 CHO cells or hippocampal neurons expressing MARCKS as a fusion protein with green fluorescent protei

54 comes more favorable when: 1), Lys-13 and FA-MARCKS(151-175) sequester several PI(4,5)P2; 2), the lin

55 sorbed basic peptides: Lys-7, Lys-13, and FA-MARCKS(151-175), a peptide based on MARCKS(151-175).

56 ed for membrane association is essential for MARCKS function in radial glia.

57 r cells were pharmacologically inhibited for MARCKS activity and subjected to functional bioassays.

58 a and the Rho/ROK pathways are necessary for MARCKS activation.

59 that an atypical isoform was responsible for MARCKS phosphorylation.

60 Our findings establish a distinct role for MARCKS in the regulation of H(2)O(2)-induced permeabilit

61 These results suggest a key role for MARCKS PSD in cancer disease and provide a unique strate

62 These results indicate a crucial role for MARCKS, specifically its phosphorylated form, in potenti

63 ect role of MARCKS in proplatelet formation; MARCKS KO MKs displayed significantly decreased proplate

64 ts from MARCKS and release of PI(4,5)P2 from MARCKS; PI(4,5)P2 subsequently binds to TRPC1 subunits t

65 h causes dissociation of TRPC1 subunits from MARCKS and release of PI(4,5)P2 from MARCKS; PI(4,5)P2 s

66 We further demonstrated that higher MARCKS expression promotes growth and angiogenesis in vi

67 ever, behavioral consequences of hippocampal MARCKS peptide infusions have not been investigated.

68 d Phe residues play an essential role in how MARCKS-ED detects and binds to curved bilayers.

69 substrate and confirm previously identified MARCKS as a a bona fide Cdk5 substrate.

70 These data identify MARCKS as a pathogenic contributor to IH and indicate th

71 We aimed to determine if MARCKS PSD activity can serve as a therapeutic target an

72 MARCKS inhibited apoE secretion, implicating MARCKS as a downstream effector of PKC in apoE secretion

73 The critical role of PIP(2) in MARCKS responses was explored by examining the PIP(2)- a

74 TLC failed to increase MARCKS phosphorylation in HuH-NTCP cells transfected wit

75 ion-deficient MARCKS, TLC failed to increase MARCKS phosphorylation or decrease PM-MRP2.

76 TLC, but not cAMP, increased MARCKS phosphorylation in HuH-NTCP cells and hepatocytes

77 methacrylate (PMA), which markedly increased MARCKS phosphorylation while significantly inhibiting pr

78 Intact MARCKS also does not bind as well to calmodulin as does

79 , yet paradoxically, we now find that intact MARCKS does not bind to actin.

80 e bilayer similar to that of the full-length MARCKS-ED peptide.

81 de comprising the effector domain of MARCKS (MARCKS-ED).

82 induced MRP2 retrieval involves PKC-mediated MARCKS phosphorylation.

83 s were markedly attenuated by siRNA-mediated MARCKS knockdown.

84 horylation of downstream signaling molecules MARCKS and PKCmu.

85 Moreover, MARCKS knockdown effectively abrogated N-WASP activation

86 singly, attenuation of MARCKS using the MPS (MARCKS phosphorylation site domain) peptide synergistica

87 ression of phosphorylation-deficient, mutant MARCKS greatly expands growth cone adhesion, and this is

88 Cells expressing this mutated MARCKS-ED SA4 show delayed onset of antigen-stimulated C

89 2.08 x 10(-7)), and rs7765004 at 6q21 (near MARCKS and HDAC2; HR, 1.38; 95% CI, 1.22 to 1.57; P = 7.

90 Nonphosphorylatable MARCKS caused spine elongation and increased the mobilit

91 However, myosin II, but not MARCKS, is required for the activity-dependent exocytosi

92 R4 signaling was enhanced by the ablation of MARCKS, which had no effect on stimulation by TLR2, TLR3

93 Here, we demonstrate that activation of MARCKS protein is important for PMA- and bombesin (BBS)-

94 ique strategy for inhibiting the activity of MARCKS PSD as a treatment for lung cancer.

95 o bind to actin and increase the affinity of MARCKS for calmodulin.

96 Surprisingly, attenuation of MARCKS using the MPS (MARCKS phosphorylation site domain

97 These results show the capacity of MARCKS-ED to regulate granule exocytosis in a PKC-depend

98 oth myristoylation of MARCKS and cleavage of MARCKS by calpain are shown to increase the availability

99 characterized by extensive colocalization of MARCKS and alpha3-integrin, resistance to eicosanoid-tri

100 H and examine the phenotypic consequences of MARCKS silencing by small interfering RNA (siRNA) transf

101 Our data suggest a major contribution of MARCKS to kidney cancer growth and provide an alternativ

102 Immunoblots confirm the degradation of MARCKS and fascin after preconditioning ischemia.

103 phosphorylation and consequent detachment of MARCKS from the membrane.

104 a peptide comprising the effector domain of MARCKS (MARCKS-ED).

105 e notion that PSA and the effector domain of MARCKS interact at and/or within the plane of the membra

106 By contrast, the myristoylation domain of MARCKS needed for membrane association is essential for

107 ng hypothesis is that the effector domain of MARCKS reversibly sequesters a significant fraction of t

108 a peptide comprising the effector domain of MARCKS the EPR spectrum broadens, but the changes in lin

109 S binding site within the effector domain of MARCKS was narrowed down to a heptapeptide that binds to

110 ctions between oppositely charged domains of MARCKS were responsible for long-range interactions with

111 ection technique to determine the effects of MARCKS silencing in human saphenous vein cultured ex viv

112 75) and short (amino acids 159-165) forms of MARCKS peptides could affect memory performance in the 1

113 e-sensing capabilities of seven fragments of MARCKS-ED.

114 However, the functionality of MARCKS and its related phosphorylation in lung cancer ma

115 A-NCAM) with MARCKS and co-immunostaining of MARCKS and PSA at the cell membrane of hippocampal neuro

116 hese cells, and direct peptide inhibition of MARCKS inhibited apoE secretion, implicating MARCKS as a

117 imilarly, small interfering RNA knockdown of MARCKS also increased LPS signaling, whereas overexpress

118 siRNA knockdown of MARCKS expression in these highly invasive lung cancer c

119 We found that siRNA-mediated knockdown of MARCKS in cultured endothelial cells abrogated directed

120 Following knockdown of MARCKS in RCC cells, the IC50 of the multikinase inhibit

121 siRNA-mediated knockdown of MARCKS or Rac1 attenuates receptor-mediated activation o

122 ) was blocked by siRNA-mediated knockdown of MARCKS, as determined using both biochemical assays and

123 This study demonstrated elevated levels of MARCKS and phospho-MARCKS in highly invasive lung cancer

124 le spinning NMR to establish the location of MARCKS-(151-175) in membrane bilayers, which is necessar

125 Loss of MARCKS results in ectopic collection of mitotically acti

126 ply that post-translational modifications of MARCKS are necessary and sufficient to regulate actin-bi

127 h this hypothesis, chemical modifications of MARCKS that neutralize negatively charged residues outsi

128 Similarly, both myristoylation of MARCKS and cleavage of MARCKS by calpain are shown to in

129 sed LPS signaling, whereas overexpression of MARCKS inhibited LPS signaling.

130 r Ca(2+)-PKC and the PIP2-binding peptide of MARCKS modulate the level of free PIP2, which serves as

131 trate, surprisingly, that phosphorylation of MARCKS by PKC is not essential for the role of MARCKS in

132 is suggested PKC-mediated phosphorylation of MARCKS by TLC.

133 Phosphorylation of MARCKS causes its translocation from the membrane to the

134 Because phosphorylation of MARCKS modulates its actin crosslinking function, this l

135 duced mucin secretion and phosphorylation of MARCKS, whereas transfection of a wild-type construct in

136 dose- and time-dependent phosphorylation of MARCKS.

137 I3K), and subsequently to phosphorylation of MARCKS.

138 lso substantially reduced in the presence of MARCKS-ED SA4, but store-operated Ca(2+) entry is not in

139 ways, including the sequential regulation of MARCKS activity by Rho/ROK and PKC-delta proteins, in st

140 etion by airway epithelium via regulation of MARCKS phosphorylation.

141 experiments show that the five Phe rings of MARCKS-(151-175) penetrate into the acyl chain region of

142 We investigated the role of MARCKS (myristoylated, alanine-rich C-kinase substrate)

143 ll imaging approaches to explore the role of MARCKS in endothelial signal transduction pathways activ

144 The role of MARCKS in endothelial signaling responses is incompletel

145 Here, we further characterize the role of MARCKS in IH and examine the phenotypic consequences of

146 by C3 toxin, demonstrating that the role of MARCKS in NT secretion was regulated by PKC-delta downst

147 ockout (KO) mice to probe the direct role of MARCKS in proplatelet formation; MARCKS KO MKs displayed

148 RCKS by PKC is not essential for the role of MARCKS in radial glial cell development.

149 To examine the role of MARCKS in the PKC pathway, we treated MKs with polymetha

150 Because of the unusual primary sequence of MARCKS with an overall isoelectric point of 4.2 yet a ve

151 ments were taken from the central stretch of MARCKS-ED.

152 Genetic and pharmacologic suppression of MARCKS in high-grade RCC cell lines in vitro led to a de

153 ase of E-cadherin expression, suppression of MARCKS phosphorylation and AKT/Slug signalling pathway b

154 The membrane-associated targeting of MARCKS and the resultant polarized distribution of signa

155 Transcription of MARCKS is increased by stimulation with bacterial LPS.

156 ces the phosphorylation and translocation of MARCKS from the cell membrane to the cytosol.

157 on/metastasis and suggest a potential use of MARCKS-related peptides in the treatment of lung cancer

158 Calmodulin acting at, or upstream of, MARCKS is also required for TRPC1 channel opening throug

159 , and FA-MARCKS(151-175), a peptide based on MARCKS(151-175).

160 ovel pathway that is critically dependent on MARCKS, Rac1, and c-Abl.

161 angiotensin-II PIP(2) regulation depends on MARCKS and H(2)O(2).

162 uct did not affect either mucin secretion or MARCKS phosphorylation.

163 p-MARCKS also was enriched in the periphery of the actin c

164 Akt kinase activity, as well as downstream p-MARCKS and ribosomal p-S6.

165 e examined temporal and spatial changes in p-MARCKS localization during maturation of mouse oocytes a

166 ing revealed that the staining patterns of p-MARCKS and the active form of the atypical PKC zeta/lamb

167 KC isoforms did not increase the amount of p-MARCKS suggested that an atypical isoform was responsibl

168 Like pericentrin, p-MARCKS staining at the MI spindle poles was asymmetric.

169 nking function, this localization suggests p-MARCKS functions as part of the contractile apparatus du

170 however, the spindle poles had symmetrical p-MARCKS staining.

171 These results show that p-MARCKS is a novel centrosome component and also defines

172 maturation of mouse oocytes and found that p-MARCKS is a novel centrosome component based its co-loca

173 the association of a 25-amino-acid peptide, MARCKS-ED, to membranes with and without spin labels.

174 ins 13 basic residues and 5 phenylalanines), MARCKS-(151-175), laterally sequester the polyvalent lip

175 trated elevated levels of MARCKS and phospho-MARCKS in highly invasive lung cancer cell lines and lun

176 63A) MARCKS, we showed that elevated phospho-MARCKS promoted cancer growth and erlotinib resistance.

177 We demonstrated that higher phospho-MARCKS levels were correlated with shorter overall survi

178 Interestingly, phospho-MARCKS acted in parallel with increased phosphatidylinos

179 The clinical relevance of phospho-MARCKS was first confirmed.

180 tasis in vivo, and reduced levels of phospho-MARCKS, phosphatidylinositol (3,4,5)-triphosphate, and A

181 tionality and molecular mechanism of phospho-MARCKS.

182 ted alanine-rich C kinase substrate (phospho-MARCKS) at the phosphorylation site domain (PSD) is cruc

183 e 3-kinase with MARCKS, but not with phospho-MARCKS.

184 edema, this binding stabilizes the ENaC-PIP2-MARCKS complex, which is necessary for the open probabil

185 We investigated this hypothesized Ca(2+)-PKC-MARCKS-PIP2-PI3K-PIP3 amplification module and tested it

186 These findings 1) show that the Ca(2+)-PKC-MARCKS-PIP2-PI3K-PIP3 system functions as an activation

187 increased cytosolic pMARCKS and decreased PM-MARCKS in HuH-NTCP cells.

188 n endothelial cells, angiotensin-II-promoted MARCKS phosphorylation is abrogated by PEG-catalase, imp

189 ted alanine-rich C-kinase substrate protein (MARCKS), a prominent cellular substrate for PKC, modulat

190 ted proteins we characterized two proteins, :MARCKS (Myristoylated Alanine-Rich protein Kinase C subs

191 Moreover, expression of pseudophosphorylated MARCKS was, by itself, sufficient to induce spine loss a

192 ve hospitalization data suggests SAT1, PTEN, MARCKS and MAP3K3 might be not only state biomarkers but

193 y transfer from Bodipy-TMR-PIP2 to Texas Red MARCKS(151-175) adsorbed to large unilamellar vesicles.

194 published biomarkers for suicidality (SAT1, MARCKS and SKA2).

195 rted by Gay et al. that long, but not short, MARCKS peptides inhibit alpha7 nAChRs.

196 The shorter MARCKS peptide did not affect memory performance.

197 readily translated to the clinic to silence MARCKS in vein bypass grafts prior to implantation.

198 Silencing MARCKS expression dramatically reduces growth cone sprea

199 in releasing peptide, demonstrated a similar MARCKS phosphorylation as noted with PMA.

200 Similarly, MARCKS-ED tagged with monomeric red fluorescent protein

201 1 knockdown blocks angiotensin-II-stimulated MARCKS phosphorylation.

202 After LPS stimulation, MARCKS moved from the plasma membrane to FYVE-positive e

203 ntified the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) a

204 ted alanine-rich protein kinase C substrate (MARCKS) correlated with modulation of PKC activity in th

205 ted alanine-rich protein kinase C substrate (MARCKS) is a cellular substrate for protein kinase C (PK

206 ted alanine-rich protein kinase C substrate (MARCKS) may function to sequester phosphoinositides with

207 ted alanine-rich protein kinase C substrate (MARCKS) sequesters phosphoinositides at the inner leafle

208 ted alanine-rich protein kinase C substrate (MARCKS), and mitogen-activated protein kinase kinase kin

209 istoylated, alanine-rich C-kinase substrate (MARCKS) and fascin.

210 ristoylated alanine-rich C-kinase substrate (MARCKS) and LAMC2 protein level were increased with AKT1

211 ristoylated alanine-rich C kinase substrate (MARCKS) and release phosphatidylinositol-4,5-bisphosphat

212 ristoylated alanine-rich C kinase substrate (MARCKS) and these effects were abolished by ketanserin a

213 ristoylated alanine-rich C-kinase substrate (MARCKS) as a key mediator of the H(2)O(2)-induced permea

214 ristoylated alanine-rich C kinase substrate (MARCKS) as novel PSA binding partner.

215 ristoylated alanine-rich C-kinase substrate (MARCKS) bind to phosphatidylserine exposed on activated

216 ristoylated alanine-rich C kinase substrate (MARCKS) binds strongly to membranes containing phosphati

217 ristoylated alanine-rich C-kinase substrate (MARCKS) in this process.

218 ristoylated alanine-rich C kinase substrate (MARCKS) is a membrane-bound F-actin crosslinking protein

219 ristoylated alanine-rich C kinase substrate (MARCKS) is an intrinsically unfolded protein with a cons

220 ristoylated alanine-rich C kinase substrate (MARCKS) is an unfolded protein that contains well charac

221 ristoylated alanine-rich C kinase substrate (MARCKS) may have a role in regulating the level of free

222 ristoylated alanine-rich C-kinase substrate (MARCKS) motif of DGKzeta, we tested whether this modific

223 ristoylated alanine-rich C kinase substrate (MARCKS) peptide comprising the phosphorylation site or e

224 ristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation site domain (PSD) in DGK zeta wa

225 ristoylated alanine-rich C kinase substrate (MARCKS) protein coordinates activation of TRPC1 channels

226 ristoylated alanine-rich C kinase substrate (MARCKS) protein in these cells.

227 ristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the

228 ristoylated alanine-rich C kinase substrate (MARCKS), a key protein kinase C (PKC) substrate, to be u

229 ristoylated alanine-rich C kinase substrate (MARCKS), a major protein kinase C substrate, binds elect

230 ristoylated Alanine-Rich C Kinase Substrate (MARCKS), a substrate of protein kinase C, is a key regul

231 ristoylated alanine-rich C kinase substrate (MARCKS), or a peptide corresponding to this domain, MARC

232 ristoylated alanine-rich C-kinase substrate (MARCKS), which was upregulated 3.4- and 5.7-fold in prop

233 istoylated, alanine-rich C-kinase substrate (MARCKS).

234 yristolated alanine-rich C-kinase substrate (MARCKS).

235 ristoylated alanine-rich C-kinase substrate (MARCKS-ED) has been demonstrated to have curvature-sensi

236 ristoylated alanine-rich C-kinase substrate (MARCKS-ED) is a highly basic, unstructured protein segme

237 lose proximity when bound to MARCKS and that MARCKS associates with multiple PI(4,5)P(2) molecules.

238 s necessary for growth cone turning and that MARCKS, while at the membrane, colocalizes with alpha3-i

239 We conclude that MARCKS is involved in regulating growth cone adhesion as

240 undant evidence supports the conclusion that MARCKS is an important protein in regulating actin dynam

241 These findings demonstrate that MARCKS contributes to the negative regulation of the cel

242 Our data demonstrate that MARCKS phosphorylation under elevated cell firing is req

243 We determined that MARCKS and MARCKS-related protein specifically bind to L

244 We find that MARCKS-ED dissociation is prevented by mutation of four

245 les from 56 patients with RCC, we found that MARCKS expression and its phosphorylation are increased

246 data are consistent with the hypothesis that MARCKS functions to sequester multiple PI(4,5)P(2) molec

247 We hypothesized that MARCKS phosphorylation promotes Arp2/3 phosphorylation,

248 We propose that MARCKS acts as a "molecular switch," binding to and regu

249 ng and hydrodynamic approaches revealed that MARCKS is targeted to plasmalemmal caveolae and undergoe

250 These novel findings show that MARCKS coordinates native TRPC1 channel activation in VS

251 Here we show that MARCKS is expressed in intact arterial preparations, wit

252 Taken together, these studies show that MARCKS plays a key role in insulin-dependent endothelial

253 g proplatelet formation 84%, suggesting that MARCKS phosphorylation reduces proplatelet formation.

254 The MARCKS peptides antagonize the binding of factor Xa to p

255 The MARCKS protein (myristoylated alanine-rich C kinase subs

256 The MARCKS-ED peptide abolished PSA-induced enhancement of n

257 ate that highly charged peptides such as the MARCKS-ED penetrate the membrane interface with aromatic

258 Both the MARCKS protein and a peptide corresponding to the effect

259 Consistent with pelleting data, the MARCKS peptide showed preference for the Ld domain.

260 In whole blood under flow, the MARCKS peptides colocalize with, and inhibit fibrin cros

261 e off state of the amplification module, the MARCKS peptide sequesters PIP2 and thereby inhibits PI3K

262 lly bind to LPS and that the addition of the MARCKS effector peptide inhibited LPS-induced production

263 y assays, meanwhile, reveal that five of the MARCKS fragments possess the ability to sense membrane c

264 The deep location of the MARCKS peptide in the polar head group region should enh

265 on state, Ca(2+)-PKC phosphorylation of the MARCKS peptide reverses the PIP2 sequestration, thereby

266 We also found that the effect of the MARCKS(151-175) peptide was dose-dependent, with a robus

267 icate that the phenylalanine residues of the MARCKS-ED are positioned within the membrane hydrocarbon

268 Research of the MARCKS-ED has further revealed that its Lys and Phe resi

269 ce and may play a role in the ability of the MARCKS-ED to sequester polyphosphoinositides.

270 Here, the position of the MARCKS-ED was determined when bound to phospholipid bice

271 results suggest that by phosphorylating the MARCKS PSD, PKC alpha attenuates DGK zeta activity.

272 reatment with a 25-mer peptide targeting the MARCKS PSD motif (MPS peptide), we were able to suppress

273 In vivo, we find that the MARCKS peptides circulate to remote injuries and bind to

274 y, treatment with a peptide identical to the MARCKS N-terminus sequence (the MANS peptide) impaired c

275 inal targeting region have similarity to the MARCKS proteins and were found to control AKAP12 localiz

276 ted and unsaturated acyl chains, whereas the MARCKS peptide and Evectin2 preferentially bound to memb

277 hosphorylated DGK zeta on serines within the MARCKS PSD in vitro and in vivo.

278 t (DGK zeta S/D) in which serines within the MARCKS PSD were altered to aspartates (to mimic phosphor

279 c contributor to IH and indicate therapeutic MARCKS silencing could selectively suppress the "atherog

280 Thus, MARCKS is a key factor in the maintenance of dendritic s

281 he N terminus alters how calmodulin binds to MARCKS, implying that, despite its unfolded state, the d

282 -PIP(2) are in close proximity when bound to MARCKS and that MARCKS associates with multiple PI(4,5)P

283 signaling complexes with PI(4,5)P2 bound to MARCKS; in this configuration TRPC1 channels are closed.

284 a that is triggered by H(2)O(2) and leads to MARCKS phosphorylation.

285 Small interfering RNA (siRNA) to MARCKS significantly inhibited, whereas overexpression o

286 the free PSD binds with site specificity to MARCKS, suggesting that long-range intramolecular intera

287 ling pathway but not the expression of total MARCKS.

288 spread, whereas overexpression of wild-type MARCKS inhibits growth cone collapse triggered by PKC ac

289 hibited, whereas overexpression of wild-type MARCKS significantly increased PMA-mediated NT secretion

290 d green fluorescent protein-tagged wild-type MARCKS were translocated from membrane to cytosol upon P

291 ce spectra of spin-labeled PIP2 as unlabeled MARCKS(151-175) adsorbs to vesicles.

292 in large unilamellar vesicles when unlabeled MARCKS(151-175) binds to vesicles.

293 e inner leaflet of the plasma membrane until MARCKS dissociates after phosphorylation by activated PK

294 Finally, we used MARCKS knockout (KO) mice to probe the direct role of MA

295 Compound 8 interfered with MARCKS phosphorylation and TPA-induced translocation of

296 nteraction of phosphoinositide 3-kinase with MARCKS, but not with phospho-MARCKS.

297 anging) and reference (constant) memory with MARCKS(151-175) only.

298 eural cell adhesion molecule (PSA-NCAM) with MARCKS and co-immunostaining of MARCKS and PSA at the ce

299 primary hippocampal neurons transfected with MARCKS.

300 ong-range intramolecular interactions within MARCKS are also possible.

301 sponsible for long-range interactions within MARCKS that sterically influence binding events at the P