ライフサイエンスコーパス: aPKC

1 aPKC adopts a polarised localisation in PrE cells only a

2 aPKC associated with Mst1/2, which uncoupled Mst1/2 from

3 aPKC-iota/lambda and its polarity signalling partners co

4 aPKC-iota/lambda functions downstream of SMO to phosphor

5 aPKC-lambda has recently been implicated in epidermal di

6 aPKC-lambda, as well as Par3, localizes at the presumpti

7 osed of the proteins Par-6, Bazooka (Par-3), aPKC, and Cdc42, is best known for roles in asymmetric c

8 on without affecting its expression or Par-3/aPKC lambda binding.

9 e anterior/lateral localisation of the Par-6/aPKC complex and the posterior recruitment of Par-1, whi

10 or axis of the oocyte by targeting the Par-6/aPKC complex for degradation at the oocyte posterior.

11 The Par-6/aPKC complex is ectopically localised to the posterior o

12 The Par-3/Par-6/aPKC complex is the primary determinant of apical polari

13 phila neuroblasts, the Inscuteable/Baz/Par-6/aPKC complex recruits Pins apically to induce vertical s

14 Aberrant aPKC activity disrupts polarity, yet the mechanisms that

15 polarize cells, these proteins must activate aPKC within a spatially defined membrane domain on one s

16 Activated aPKC-iota/lambda is upregulated in SMO-inhibitor-resista

17 to phosphorylation by mitotically activated aPKC kinase and thought to promote asymmetric cell divis

18 Overexpression of activated aPKC blocks the neuronal differentiation-promoting activ

19 localization, Par-6 allosterically activates aPKC to allow for high spatial and temporal control of s

20 dimerization, and this interaction activates aPKC by displacing the pseudosubstrate, although full ac

21 How PIP3 activates aPKC is unknown.

22 Active aPKC increases Pins phosphorylation on Ser401, which rec

23 ontrast, expression of constitutively active aPKC elevates basolateral accumulation of Smo and promot

24 d by overexpression of constitutively active aPKC.

25 6, vang, pk, and fmi are upregulated, and an aPKC mutation suppresses the Rbf1-induced phenotypes.

26 lpha (TNFalpha) is necessary for iPMF via an aPKC-dependent mechanism.

27 Incubation with an aPKC pseudosubstrate recapitulates the phenotype of PKCi

28 on with junctional components; the tjp-2 and aPKC mRNA-rescued embryos also had 24 and 45% decreases

29 In contrast, we find that while Par-6 and aPKC are both required for subcellular lumen formation,

30 Par-6 and aPKC interact via PB1 domain heterodimerization, and thi

31 a nor a direct interaction between Par-6 and aPKC is needed for this process.

32 cal role for the polarity proteins Par-6 and aPKC is used in formation of this subcellular apical com

33 a complex of Bazooka (Baz; Par-3), Par-6 and aPKC marking the anterior and lateral cortex, and Par-1

34 Bazooka (PAR-3), PAR-6, and aPKC form a complex that plays a key role in the polariz

35 In T2DM, whereas Akt and aPKC activation are diminished in muscle, and hepatic Ak

36 Additionally, Akt and aPKC activities in muscle improved, as did glucose intol

37 resting/basal and insulin-stimulated Akt and aPKC activities were diminished in muscle, but in liver,

38 uestered to cell-cell junctions by Amot, and aPKC overexpression resulted in loss of Amot expression

39 Both Bazooka and aPKC regulate Canoe localization despite being "downstre

40 We find Par-6, Bazooka, and aPKC, as well as known interactions between them, are re

41 Further, Rap1, Bazooka, and aPKC, but not Canoe, regulate columnar cell shape.

42 We searched for overlapping BH and aPKC phosphorylation site motifs (i.e., putative phospho

43 ng the formation of a cable where Crumbs and aPKC are localized.

44 ts divisions, but Inscuteable expression and aPKC, dlg and pins mutants have no effect.

45 ncident manner by both JNK-dependent Fos and aPKC-mediated Yki transcription.

46 reciprocal interactions between Crb, Moe and aPKC during cellular morphogenesis.

47 Furthermore, Moe and aPKC functioned antagonistically, suggesting that Moe li

48 lin promotes the association of both p62 and aPKC with the insulin-regulated scaffold IRS-1.

49 of cell polarity molecules such as Par3 and aPKC and cell compaction at the 8- and 16-cell stages.

50 Specifically, we show that Par3 and aPKC promote the apical positioning of centrioles, where

51 ymmetry in various systems, whereas Par3 and aPKC/Par6 can also act independently.

52 larity complex consisting of par3, par6, and aPKC.

53 We conclude that Par6B and aPKC control mitotic spindle orientation in polarized ep

54 Mechanistically, Par6B and aPKC function interdependently in this context.

55 Our results suggest that Rab14 and aPKC interact to regulate trafficking of claudin-2 out o

56 n the oocyte, shows that maternal Vangl2 and aPKC are required for specific oocyte asymmetries and ve

57 Thus, Yrt and aPKC are involved in a reciprocal antagonistic regulator

58 sults reveal how Par3/Baz CR3 can antagonize aPKC in stable apical Par complexes and suggests that mo

59 ises the anti-neurogenic influence of apical aPKC by physically partitioning cells away from it in vi

60 Slmb function is required to restrain apical aPKC activity in a manner that is independent of endolys

61 we show that Baz is excluded from the apical aPKC domain in epithelia by aPKC phosphorylation, which

62 gulator for TrkB and as a scaffold for aPKC (aPKC).

63 aPKC phosphorylation, which disrupts the Baz/aPKC interaction.

64 agonistic intermolecular competition between aPKC isoforms directs the establishment of neuronal pola

65 unctional complex, especially aPKC, and both aPKC and Bves are indispensable to claudin expression.

66 Here, we show that deletion of both aPKC isoforms resulted in a deficit in asymmetric divisi

67 y by controlling the phosphorylation of both aPKC isoforms.

68 osphorylation experiments revealed that both aPKC isoforms were substrates of PHLPP.

69 o sorting into the retromer pathway via both aPKC-dependent and -independent mechanisms.

70 e 2 leads to translocation of membrane-bound aPKC to the cytosol, concurrent with its activation and

71 tex but were displaced into the cytoplasm by aPKC.

72 from the apical aPKC domain in epithelia by aPKC phosphorylation, which disrupts the Baz/aPKC intera

73 and assembly of zBves were not influenced by aPKC-MO.

74 ted potential independently of regulation by aPKC.

75 iPMF requires atypical protein kinase C (aPKC) activity within spinal segments containing the phr

76 through Cdc42 and atypical protein kinase C (aPKC) also cause spindle misorientation.

77 ling intermediate atypical protein kinase C (aPKC) constrains food intake, weight gain, and glucose i

78 Atypical protein kinase C (aPKC) controls cell polarity by modulating substrate cor

79 larvae (Lgl) and atypical Protein Kinase C (aPKC) ensures self-renewal of a daughter neuroblast and

80 Atypical protein kinase C (aPKC) enzymes signal on protein scaffolds, yet how they

81 AR-6, CDC-42, and atypical protein kinase C (aPKC) form a core unit of the PAR protein network, which

82 naling to Akt and atypical protein kinase C (aPKC) in liver and muscle and hepatic enzyme expression

83 ulin signaling to atypical protein kinase C (aPKC) in muscle and liver that generate cardiovascular r

84 Atypical protein kinase C (aPKC) is a key apical-basal polarity determinant and Par

85 Activity of the atypical protein kinase C (aPKC) is a key output of the Par complex as phosphorylat

86 suggests that the atypical Protein Kinase C (aPKC) is a key regulator of cell fate decisions in metaz

87 The atypical protein kinase C (aPKC) is a key regulator of polarity and cell fate in lo

88 al loss of either atypical protein kinase C (aPKC) isoform, PKCzeta or PKClambda/iota, partially impa

89 Atypical protein kinase C (aPKC) isoforms are overexpressed and activated in many c

90 Atypical protein kinase C (aPKC) isoforms zeta and lambda interact with polarity co

91 The atypical protein kinase C (aPKC) isotypes PKClambda/iota and PKCzeta are both expre

92 Atypical protein kinase C (aPKC) isozymes modulate insulin signaling and cell polar

93 fy the Cdc42/Par6/atypical protein kinase C (aPKC) Par polarity complex as uniquely and specifically

94 r, we report that atypical protein kinase C (aPKC) phosphorylates Yrt to prevent its premature apical

95 nserved Par3/Par6/atypical protein kinase C (aPKC) polarity cassette that restricts migration of baso

96 ctor complex Par6-atypical protein kinase c (aPKC) regulate multiple steps during epithelial differen

97 complex component atypical Protein Kinase C (aPKC) to the essential spindle orientation factor GukHol

98 ere, we show that atypical protein kinase C (aPKC), a protein associated with apicobasal polarity, is

99 binding partner, atypical protein kinase C (aPKC), are required to regulate Caco-2 morphogenesis.

100 kinases, Akt and atypical protein kinase C (aPKC), were maximally increased.

101 The protein atypical protein kinase C (aPKC)--a component of the Par complex, which localizes t

102 The PAR-3-atypical protein kinase C (aPKC)-PAR-6 complex has been implicated in the developme

103 ens junctions and atypical protein kinase C (aPKC).

104 al maintenance of atypical protein kinase C (aPKC).

105 file of proteins (atypical protein kinase C [aPKC], Cdc42, Sec8, Rab11a, and Rab8) and ceramide speci

106 ical actin nucleation that depends on Cdc42, aPKC, and Par6.

107 actions, recruitment of Sdt-aPKC-Par6-cdc42, aPKC phosphorylation of Crb, and recruitment of Expanded

108 to more lateral cell surfaces enables Cdc42/aPKC/Par6 to take on a mitosis-specific function-aiding

109 determines spatiotemporal patterns of Cdc42/aPKC activation during endothelial morphogenesis.

110 Pharmacological inhibition of CNS aPKC activity acutely increases food intake and worsens

111 increases in activity of cocompartmentalized aPKC.

112 angl2 and the apical-basal complex component aPKC.

113 of the polarity complex signaling component aPKC, thereby regulating myelin formation.

114 In contrast, aPKC activity associated with WD40/ProF was increased.

115 ong with the molecular pathways that control aPKC and those that are responsive to changes in its cat

116 ts polarity, yet the mechanisms that control aPKC remain poorly understood.

117 ts previously described roles in controlling aPKC localization, Par-6 allosterically activates aPKC t

118 Conversely, aPKC protects Par6B from proteasomal degradation, in a k

119 e absence of lgl function, elevated cortical aPKC kinase activity perturbs unequal partitioning of th

120 To investigate how increased cortical aPKC function induces formation of excess neuroblasts, w

121 neuroblasts triggered by increased cortical aPKC function.

122 propose that precise regulation of cortical aPKC kinase activity distinguishes the sibling cell iden

123 In return, Yrt counteracts aPKC functions to prevent apicalization of the plasma me

124 In 2D cultures, aPKC induced cells to grow as stratified epithelia, wher

125 de prevents activation of HDAC6 by cytosolic aPKC and AurA, which promotes acetylation of tubulin in

126 Defective aPKC signaling results in a dramatically simplified glom

127 Thus, Numb promotes BDNF-dependent aPKC activation.

128 Silencing of Par3 also disrupts aPKC association with the apical cortex, but expression

129 idues in the Akt pleckstrin homology domain, aPKCs lack this domain.

130 hese results led us to propose that elevated aPKC function in the cortex of mitotic neuroblasts reduc

131 ic alternative transcript, and Prkcl encodes aPKC-lambda.

132 Prkcz encodes aPKC-zeta and PKM-zeta, a truncated, neuron-specific alt

133 We conclude that epithelial aPKC acts upstream of multiple mechanisms that participa

134 ay of the PAR junctional complex, especially aPKC, and both aPKC and Bves are indispensable to claudi

135 rk has implicated the apical polarity factor aPKC, the junctional protein APC2, and basal integrins i

136 RECENT FINDINGS: aPKC and Akt mediate the insulin effects on glucose tran

137 Of importance, Yap1 was necessary for aPKC-mediated overgrowth but did not restore cell polari

138 tic regulator for TrkB and as a scaffold for aPKC (aPKC).

139 A form of Lgl that is a substrate for aPKC, but not Aurora kinases, can restore cell polarity

140 We achieved full aPKC down-regulation in small intestine villi and colon

141 Furthermore, aPKC and other apical polarity factors disappear from th

142 Furthermore, aPKC-deficient podocytes failed to form the normal netwo

143 Key polarity genes aPKC, par6, vang, pk, and fmi are upregulated, and an aP

144 ortical polarity pathway (NuMA, p150(glued), aPKC).

145 Hepatic aPKC is a unifying target for treating multiple clinical

146 Imbalance between muscle and hepatic aPKC activation (and expression of PKC-iota in humans) b

147 epatic Akt activation is diminished, hepatic aPKC activation is conserved.

148 of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, bra

149 Indeed, selective inhibition of hepatic aPKC by adenoviral-mediated expression of kinase-inactiv

150 Conserved activation of hepatic aPKC in hyperinsulinemic states of T2DM, obesity and Met

151 Moreover, inhibition of hepatic aPKC reduced its association with WD40/ProF, restored WD

152 gation of aPKC toward the anterior but holds aPKC in an inactive state, and a CDC-42-dependent assemb

153 These data implicate aPKC as a novel regulator of energy and glucose homeosta

154 al for HH-dependent processes and implicates aPKC-iota/lambda as a new, tumour-selective therapeutic

155 xpression of PHLPP resulted in a decrease in aPKC phosphorylation at both the activation loop and the

156 viral-mediated expression of kinase-inactive aPKC, or newly developed small-molecule biochemicals, dr

157 ry neuroblast phenotype induced by increased aPKC function.

158 es; conversely, knockdown of PHLPP increased aPKC phosphorylation.

159 However, whether increased aPKC function triggers formation of excess neuroblasts b

160 aPKC (>90%) led to loss in biguanide-induced aPKC phosphorylation, it had no effect on Met-stimulated

161 (ZIP), has been extensively used to inhibit aPKC activity; however, we have previously shown that ZI

162 member Par-6, previously thought to inhibit aPKC, is a potent activator of aPKC in our assays.

163 l cortical displacement assay to investigate aPKC regulation.

164 onic hippocampal neurons, two aPKC isoforms, aPKC-lambda and PKM-zeta, are expressed.

165 smantles the apical domain, showing that its aPKC-mediated exclusion is crucial for epithelial cell p

166 Upon recruitment to primordial junctions, aPKC phosphorylates JAM-A at S285 to promote the maturat

167 e apically localized serine/threonine kinase aPKC directly phosphorylates an N-terminal site of the c

168 th PAR-6 and PKC-3 (atypical protein kinase; aPKC) to regulate cell polarity and junction formation i

169 eraction with GukH at cortical sites lacking aPKC.

170 ntify atypical protein kinase C iota/lambda (aPKC-iota/lambda) as a novel GLI regulator in mammals.

171 thered to the acidic surface on p62, locking aPKC in an open, signaling-competent conformation.

172 strate sequence are required for maintaining aPKCs in an inactive state and are targeted by PIP3 for

173 However, whether mammalian aPKCs control stem cells and fate in vivo is not known.

174 it was necessary for MZ localization of Moe, aPKC and F-actin.

175 Moreover, aPKC has an additional positive role in Hh signaling by

176 find that the localization and activation of aPKC involve distinct, specialized aPKC-containing assem

177 ant larvae and discs large, or activation of aPKC, activates Yorkie through Jun kinase signaling, and

178 n is problematic, as excessive activation of aPKC-dependent lipogenic, gluconeogenic and proinflammat

179 ht to inhibit aPKC, is a potent activator of aPKC in our assays.

180 P does not inhibit the catalytic activity of aPKC isozymes in cells.

181 inical data reveal the concerted activity of aPKC, cortactin, and dynamin-2, which control the traffi

182 ggesting that it antagonizes the activity of aPKC.

183 studies demonstrated that the aggregation of aPKC around the cell junctions had disintegrated in zBve

184 ramide reestablishes membrane association of aPKC, restores primary cilia, and accelerates neural pro

185 Cycling of aPKC between these distinct functional assemblies, which

186 However, although cellular depletion of aPKC (>90%) led to loss in biguanide-induced aPKC phosph

187 sotropy leads to anisotropic distribution of aPKC, which in turn can negatively regulate Rok, thus pr

188 Comparable downregulation of aPKC shRNA phenocopied effects of TNF-alpha signaling, i

189 In contrast, the effect of aPKC on Hippo/Yap signaling and overgrowth in NMuMG cell

190 ation of Yap1, indicating that the effect of aPKC on transformed growth by deregulating Hippo/Yap1 si

191 Finally, increased expression of aPKC in human cancers strongly correlated with increased

192 Finally, the expression of aPKC is up-regulated by Hh signaling in a Ci-dependent m

193 zation of aPKCs and reduced the formation of aPKC-Par3 complex.

194 Inactivation of aPKC by either RNAi or a mutation inhibits Smo basolater

195 te is triggered by posterior inactivation of aPKC or activation of Par-1.

196 We show that inhibition of aPKC from the mid blastocyst stage not only prevents sor

197 n, we report that depletion or inhibition of aPKC induces robust apoptotic cell death in Caco-2 cells

198 depletion of Tuba or Cdc42 or inhibition of aPKC is caused by defective spindle orientation.

199 Inhibition of aPKC, AurA, or a downstream target of AurA, HDAC6, resto

200 e in the absence of Par3 or by inhibition of aPKC.

201 ur findings indicate a direct involvement of aPKC in Hh signaling beyond its role in cell polarity.

202 The levels of aPKC and Par-6 are significantly increased in slmb mutan

203 t in only one aPKC isoform, complete loss of aPKC unexpectedly increased CD8(+) T cell differentiatio

204 Genetic or pharmacological loss of aPKC-iota/lambda function blocks HH signalling and proli

205 mide-binding but dominant-negative mutant of aPKC suppresses ciliogenesis, indicating that the associ

206 ome of the diverse physiological outcomes of aPKC's function in differentiation, along with the molec

207 Silencing of PKM-zeta or overexpression of aPKC-lambda in hippocampal neurons alters neuronal polar

208 formin induced activation/phosphorylation of aPKC in L6 myotubes.

209 istribution are dependent on the presence of aPKC.

210 ng in displacement of the pseudosubstrate of aPKC and re-engagement in the substrate-binding cavity.

211 Finally, we show that down-regulation of aPKC, involved in cell polarity, decreases the number of

212 tion, we showed that PDK1 aids the rescue of aPKC in in vitro rephosphorylation assays using immunode

213 To assess the role of aPKC in PrE formation, we interfered with its activity u

214 y cues and promotes efficient segregation of aPKC toward the anterior but holds aPKC in an inactive s

215 ne localization, indicating sequestration of aPKC by IRS-1 away from MARK2.

216 Silencing of aPKC in invasive breast-tumor cell lines impaired the de

217 Interestingly, Numb is also a substrate of aPKC.

218 itioning depend upon different thresholds of aPKC expression, suggesting that they are controlled by

219 caffolds serving as allosteric activators of aPKCs, tethering them in an active conformation near spe

220 altered the apical membrane localization of aPKCs and reduced the formation of aPKC-Par3 complex.

221 port a model in which the pseudosubstrate of aPKCs is tethered to the acidic surface on p62, locking

222 hanism underlying the negative regulation of aPKCs remains largely unknown.

223 ional assemblies, which appears to depend on aPKC activity, effectively links cue-sensing and effecto

224 unlike CD8(+) T cells deficient in only one aPKC isoform, complete loss of aPKC unexpectedly increas

225 odulation of CR3 inhibitory arms or opposing aPKC pockets would perturb the interaction, promoting Pa

226 depleted for the apical determinants Par6 or aPKC had identical ectopic seamed tube defects.

227 Depletion or inhibition of Par6B or aPKC phenocopies the loss of Cdc42, inducing misorientat

228 larized lipid domains and failure of the Par/aPKC/Cdc42 polarity complex to localize to the apical me

229 polarity protein complexes such as the Par3-aPKC-Par6 complex and the CRB3-Pals1-PATJ complex, which

230 cal interactions occur between the PAR3-PAR6-aPKC polarity complex and phosphorylated SMAD5 at apical

231 at the cell cortex during mitosis: Par3-Par6-aPKC, which confer polarity, and Galpha(i)-LGN/AGS3-NuMA

232 rove process-specific activation of the Par6-aPKC pathway, stimulating the transition from junction f

233 cadherin) endocytosis by limiting Cdc42/Par6/aPKC complex activity.

234 Disruption of Cdc42/Par6/aPKC leads to activation of JNK through increased Rho1 a

235 regulation is disrupted, loss of Cdc42/Par6/aPKC polarity complex organization or localization could

236 d the apical recruitment of a Par3/Par6alpha/aPKC/Rac1 signaling module for a robust, spatially local

237 Paradoxically, aPKC also phosphorylates Par3/Baz, provoking its relocal

238 of the steady-state levels of atypical PKC (aPKC [PKCiota/lambda and zeta]) and is blocked in inflam

239 Atypical PKC (aPKC) isoforms are activated by the phosphatidylinositol

240 his study, we demonstrate that atypical PKC (aPKC) regulates Smo phosphorylation and basolateral accu

241 amide and its interaction with atypical PKC (aPKC), both of which distribute to the primary cilium an

242 he polarity complex made up of atypical PKC (aPKC, isoforms iota and zeta), Par6, and Par3 determine

243 Atypical PKCs (aPKCs) are implicated as key regulators of epithelial po

244 Atypical PKCs (aPKCs) have been implicated in Met-stimulated GU, and in

245 te progression are interdependent, and place aPKC as a central player in the segregation of epiblast

246 rms a tight inhibitory complex with a primed aPKC kinase domain, blocking substrate access.

247 n of PKCII, antagonist of the apical protein aPKC.

248 PDK1, pT555-aPKC, and pAkt were dependent on dynamin activity.

249 e of Caco-2 cysts and is required to recruit aPKC to this compartment.

250 identify a novel role of PHLPP in regulating aPKC and cell polarity.

251 and analyzed the stability of the remaining aPKC pool.

252 The ability of Yrt to bind and restrain aPKC signaling is central for its role in polarity, as r

253 nveils a novel mechanism by which scaffolded aPKC is maintained in an active conformation.

254 ular domain interactions, recruitment of Sdt-aPKC-Par6-cdc42, aPKC phosphorylation of Crb, and recrui

255 t of apical-basal polarity (A-BP) signaling, aPKC, also inhibits Dishevelled1-induced Frizzled3 hyper

256 ha is sufficient to elicit pMF via a similar aPKC-dependent mechanism.

257 vation of aPKC involve distinct, specialized aPKC-containing assemblies: a PAR-3-dependent assembly t

258 via a TNFalpha-dependent increase in spinal aPKC activity.

259 o iPMF, TNFalpha-induced pMF required spinal aPKC activity, as intrathecal delivery of a zeta-pseudos

260 Upstream signal(s) leading to spinal aPKC activation are unknown.

261 MO-inhibitor-resistant tumours and targeting aPKC-iota/lambda suppresses signalling and growth of res

262 Both scaffolds tether aPKC in an active conformation as assessed through pharm

263 rtex, but expression of an apically tethered aPKC rescues normal lumen formation.

264 We also demonstrate that aPKC and Vangl2 are required for the cell membrane asymm

265 These results demonstrate that aPKC-iota/lambda is critical for HH-dependent processes

266 We find that aPKC is autoinhibited by two domains within its NH(2)-te

267 n polarized epithelia and, furthermore, that aPKC coordinately regulates multiple processes to promot

268 Here we tested the hypothesis that aPKC has a dual function in epithelia, inhibiting the NF

269 elial cells (MDCK and NMuMG), we report that aPKC gain of function overcomes contact inhibited growth

270 In this paper, we show that aPKC can interact directly with JAM-A in a PAR-3-indepen

271 The results show that aPKC is dispensable for polarity after cell differentiat

272 We previously showed that aPKC is down-regulated in intestinal epithelia under inf

273 me-wide transcriptional profiling shows that aPKC-iota/lambda and SMO control the expression of simil

274 Our results suggest that aPKC isoforms orchestrate the formation of the podocyte

275 Our data suggest that aPKC phosphorylates JAM-A at S285 to regulate cell-cell

276 The aPKC defect resulted in increased NF-kappaB activity, wh

277 The aPKC-mediated phosphorylation of Smo at Ser680 promotes

278 ied by Crumbs (Crb), Stardust (Sdt), and the aPKC-Par6-cdc42 complex.

279 flanking its PKC consensus site disrupts the aPKC kinase N lobe, separating P-loop/alphaB/alphaC cont

280 -lambda for binding to Par3 and disrupts the aPKC-lambda-Par3 complex.

281 Consistent with this, overexpression of the aPKC antagonist Lgl strongly rescues the polarity defect

282 for its role in polarity, as removal of the aPKC binding site neutralizes Yrt activity.

283 Similarly, selective deletion of the aPKC isoform Pkc-lambda in proopiomelanocortin (POMC) ne

284 tially control the catalytic activity of the aPKC PKCzeta, thus promoting activity toward localized s

285 Using the aPKC substrate MARK2 as another readout for activity, we

286 he role of basic arginine residues common to aPKC pseudosubstrate sequences.

287 sors, linking BDNF, an extracellular cue, to aPKC, a critical component of the intrinsic polarity mac

288 that both classes of SMO variants respond to aPKC-iota/lambda or GLI2 inhibitors that operate downstr

289 The ACBD3 binding region of Numb harbors two aPKC phosphorylation sites, serines 48 and 52.

290 that, in embryonic hippocampal neurons, two aPKC isoforms, aPKC-lambda and PKM-zeta, are expressed.

291 that ZIP inhibits the activity of wild-type aPKC, but not a construct lacking the pseudosubstrate.

292 action and interdependence of Vangl2, VAMP1, aPKC and the stable microtubule cytoskeleton in the oocy

293 cule A (JAM-A) to primordial junctions where aPKC is activated by Rho family small guanosine triphosp

294 promote its mitotic relocalization, whereas aPKC kinase activity is required only for polarization o

295 te, and a CDC-42-dependent assembly in which aPKC is active but poorly segregated.

296 o doing, unveiled a novel mechanism by which aPKCs are maintained in an active conformation on a prot

297 cating that the association of ceramide with aPKC is critical for the formation of this complex.

298 PKM-zeta competes with aPKC-lambda for binding to Par3 and disrupts the aPKC-la

299 When co-localized with aPKC, Dlg is phosphorylated in its SH3 domain which disr

300 ly with phospholipids and also overlaps with aPKC phosphorylation sites.