ライフサイエンスコーパス: PAK

1 PAK activation increased MLC and MYPT1 phosphorylation i

2 PAK DeltafliC also inhibited NF-kappaB induced by IL-1be

3 PAK inactivation led to obliteration of social recogniti

4 PAK inhibition had the opposite results.

5 PAK inhibitors did not interfere with G protein-coupled

6 PAK is a downstream target of the neuronal Rac guanine n

7 PAK mediates both flow-induced permeability and matrix-s

8 PAK protein inhibition, in particular, markedly inactiva

9 PAK regulated MLC phosphorylation in an activity-depende

10 PAK translocated the epithelia as early as 1 hour after

11 PAK-mediated phosphorylation of PREX2 reduced GEF activi

12 PAKs are evolutionally conserved and widely expressed in

13 PAKs are subdivided into two groups: type I PAKs (PAK1,

14 TA vs. SPK, hazard ratio [HR]=2.29, P=0.020; PAK vs. SPK, HR=2.73, P=0.003) and acute pancreas reject

15 ultiinstitutional retrospective study of 126 PAK transplantation recipients who had a functioning pan

16 Pancreas graft failure occurred in 14 PAK and two PRT patients with a mean follow-up of 61.6 +

17 phosphorylation by p(21)-activated kinase 3 (PAK) and calmodulin on the 22 kDa C-terminal fragment of

18 er Shank3 knockdown, which was occluded by a PAK inhibitor.

19 5-min intracerebroventricular infusion of a PAK inhibitor peptide but not control peptide blocked ra

20 defects and conversely, overexpression of a PAK kinase was able to rescue the loss of RhoU cardiac d

21 Molecular Cell, Long et al. now show that a PAK-phosphorylated alternate-spliced isoform of the ster

22 ound that PREX2 was phosphorylated through a PAK-dependent mechanism.

23 ng dendritic spine morphology, in part via a PAK/ERK1/2-dependent pathway, and provide mechanistic in

24 Our results implicate aberrant PAK in Abeta oligomer-induced signaling and synaptic def

25 the upstream pathway by which flow activates PAK (integrin activation, Rac).

26 Whereas shear stress activates PAK in endothelial cells on a fibronectin matrix, baseme

27 by its membrane-localized upstream activator PAK.

28 This active PAK coimmunoprecipitated with the small GTPase Rac and b

29 ent for either other integrins or additional PAK family members.

30 expression of the dgcP gene in P. aeruginosa PAK led to increased exopolysaccharide production and up

31 pv. savastanoi NCPPB 3335 and P. aeruginosa PAK reduced their virulence in olive plants and in a mou

32 to the pyocin sensitive strain P. aeruginosa PAK.

33 egulon of RsmA of the Pseudomonas aeruginosa PAK strain by using cultures in the stationary phase of

34 llowing LPA stimulation, but does not affect PAK-meditated lamellipodia and filopodia formation follo

35 associated with kidney allograft loss after PAK include impaired renal function in the 3 months befo

36 All PAK recipients are alive with functioning kidney grafts,

37 thymocytes with a knockout mutation in alpha-PAK (p21-activated kinase)-interacting exchange factor (

38 between CTLA-4-PKC-eta and the GIT2-alphaPIX-PAK complex, an IS-localized focal adhesion complex.

39 vation of its downstream effectors Rac-1 and PAK were increased in the NAc of cocaine-sensitized rats

40 included 252 recipients (SPK 60, PTA 71, and PAK 121), 53% men, age 43.9+/-9 years, followed for 6.3

41 kidney, pancreas transplantation alone, and PAK transplant recipients, 54.7%, 37.3%, and 58.8% were

42 n by mediating interactions with Dock180 and PAK to bring about guanine nucleotide exchange and signa

43 cal synapse development through the EphB and PAK signaling pathways.

44 xes: (1) a complex of SCRIB, ARHGEF, GIT and PAK (p21-activated kinase), and (2) a complex of SCRIB,

45 Furthermore, survival of PAO1 and PAK strains in the cornea and development of corneal dis

46 PAO1- and PAK-infected corneas developed severe disease with prono

47 in disregulation of PDGF-stimulated Rac1 and PAK activities, reduction of Cdc42 and Erk signaling, as

48 Pancreas-graft outcomes in SPK and PAK were equivalent in our study, but our specific popul

49 Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicat

50 EphB2, Cdc42, and PAKs are broadly capable of controlling dendritic spine

51 Both SAP102 and PAKs are associated with X-linked mental retardation in

52 insulin, neuregulin, and IGF1 treatment are PAK-dependent and lead to a reduction in PREX1 binding t

53 and some of their effector proteins such as PAK and ROCK, are likely anti-cancer targets for treatin

54 paired renal function in the 3 months before PAK, proteinuria, the occurrence of a post-PAK kidney re

55 hogenesis, a complex comprising the betaPIX (PAK-interacting exchange factor beta) and class I PAKs (

56 Although a role for the Scrib-betaPIX-PAK signaling complex in promoting membrane protrusion a

57 Inhibition by PAK DeltafliC-conditioned medium was exerted from either

58 e mechanisms of PREX1 negative regulation by PAKs within receptor tyrosine kinase and GPCR-stimulated

59 and comparison subjects, and levels of CDC42-PAK-LIMK pathway messenger RNAs were measured by quantit

60 yperpermeability by activating the Rac/Cdc42/PAK pathway, with concomitant inhibition of the Rho path

61 In BRAFi-resistant cells, PAKs phosphorylate CRAF and MEK to reactivate ERK.

62 their large and flexible ATP binding cleft, PAKs, particularly group I PAKs (PAK1, -2, and -3), are

63 otected by kinase-active but not kinase-dead PAK.

64 the assembly of clathrin-coated pits, and DN PAK-1, an obligate mediator of macropinocytosis, had no

65 lopment by mediating EphB and its downstream PAK signaling pathway.

66 ntinued to recruit and activate its effector PAK, even upon serum stimulation.

67 cells on fibronectin, resulting in enhanced PAK activation, NF-kappaB phosphorylation, ICAM-1 expres

68 KA by PKA inhibitor (PKI) injection enhanced PAK activation and inflammatory gene expression.

69 , and -3), are difficult to drug; hence, few PAK inhibitors with satisfactory kinase selectivity and

70 Diabetic candidates for PAK with any of these conditions should be counseled reg

71 The most notable decrease occurred for PAK transplants, possibly due in part to decreases in nu

72 , and lack of data between kidney and PT for PAK.

73 rict IF transport and reveals a new role for PAK and ROCK in the regulation of IF precursor transport

74 e Akt, our observations support the role for PAK-1 as a potential target for therapeutic intervention

75 Pancreas graft survival was similar for PAK and PRT at 1 year (88.2% vs. 100%) and 3 years (85.1

76 outside institutions and referred to us for PAK.

77 ain PAO1, and we found that a mexS gene from PAK confers high T3SS expression in the PAO1 background.

78 present in conditioned medium isolated from PAK DeltafliC or Calu-3 plus PAK DeltafliC, but it was n

79 ium isolated from Calu-3 cells alone or from PAK DeltafliC that had been heat treated.

80 ymmetry-breaking polarization involves a GEF-PAK complex that binds GTP-Cdc42p via the PAK and promot

81 in subunits Gbeta1, Ggamma2, and/or Ggamma5, PAK-associated guanine nucleotide exchange factor (betaP

82 We propose that a Rac>PAK signaling pathway needed for rapid stabilization of

83 r(203) is mediated by kinases of the class I PAK subfamily, specifically 1) exposing cells to four st

84 of orally available ATP-competitive Group I PAK inhibitors with significant potential for the treatm

85 ies based on a benzimidazole core, a group I PAK selective series based on a pyrido[2,3-d]pyrimidine-

86 nteracting exchange factor beta) and class I PAKs (p21-activated kinases) is recruited to adherens ju

87 TP binding cleft, PAKs, particularly group I PAKs (PAK1, -2, and -3), are difficult to drug; hence, f

88 We propose a model whereby group I PAKs act downstream of Rac to organize the actin filamen

89 Group I PAKs are activated by extracellular signals through GTPa

90 identified a novel function for the group I PAKs in cell-cell fusion.

91 a potent small molecule inhibitor of group I PAKs reverses dendritic spine phenotypes in Fmr1 KO mice

92 ategy for achieving selectivity over group I PAKs, and the broad kinome, based on unique flexibility

93 We show that the two Drosophila group I PAKs, DPak3 and DPak1, have partially redundant function

94 dinone, as a potent inhibitor of the group I PAKs.

95 PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5

96 Examples are a recently discovered group II PAK (PAK4, -5, -6) selective inhibitor series based on a

97 ubstrate region, indicating a common type II PAK autoregulatory mechanism.

98 e provide a unique understanding for type II PAK regulation.

99 el details that govern regulation of type II PAK signaling.

100 t past the methionine gatekeeper of group II PAKs approached by these type I 1/2 binders were found t

101 In contrast, group II PAKs are constitutively active.

102 pe I PAKs (PAK1, PAK2, and PAK3) and type II PAKs (PAK4, PAK5, and PAK6).

103 -guided approach, we discovered that type II PAKs are regulated by an N-terminal autoinhibitory pseud

104 Dysfunction in PAK leads to cofilin activation, drebrin displacement fr

105 a-Amyloid (Abeta) oligomer was implicated in PAK defects.

106 The majority of kidney-recipients in PAK group were transplanted at outside institutions and

107 counting for the derepression of the T3SS in PAK and the dominant negative effect when it is introduc

108 he postsynaptic density disrupts DOI-induced PAK phosphorylation and spine morphogenesis.

109 Inhibiting PKA restored flow-induced PAK and NF-kappaB activation in cells on basement membra

110 ded or inflamed vessels support flow-induced PAK and NF-kappaB activation.

111 sement membrane proteins limit shear-induced PAK activation and inflammation through a protein kinase

112 Inhibiting PAK prevented the enhancement of inflammatory gene expre

113 other factors a long K to PAK time interval; PAK could be a comparable option to SPK for patients wit

114 ancreas-kidney (SPK), pancreas after kidney (PAK) and pancreas transplant alone (PTA).

115 failure subsequent to pancreas after kidney (PAK) are multifactorial; therefore, we examined these fa

116 t outcomes to primary pancreas after kidney (PAK) transplantation.

117 plantation alone, and pancreas after kidney (PAK) transplantations were performed in 42, 67, and 107

118 , and 47 pancreas transplanted after kidney [PAK]), performed at the University Hospital Innsbruck.

119 Our results demonstrate that Kif3a-PAK signaling coordinates planar polarization of the hai

120 p21-activated kinase (PAK) 2, a member of the PAK family of serine/threonine p

121 ignificant increase in p21-activated kinase (PAK) activity compared with CCS.

122 by activation of Rac1, p21-activated kinase (PAK) and AKT/protein kinase B (AKT) signaling.

123 the phosphorylation of p21-activated kinase (PAK) and extracellular signal-regulated kinase 1/2 (ERK1

124 suppress flow-induced p21 activated kinase (PAK) and nuclear factor (NF)-kappaB activation.

125 s for the RAC effector p21-activated kinase (PAK) are in late-stage clinical development and might im

126 Defects in p21-activated kinase (PAK) are suspected to play a role in cognitive symptoms

127 The p21-activated kinase (PAK) family of serine/threonine kinases is important in

128 The p21-activated kinase (PAK) family of serine/threonine protein kinases plays im

129 Activation of p21-activated kinase (PAK) followed the same matrix-dependent pattern.

130 as phosphorylation of p21-activated kinase (PAK) in cultured cortical neurons.

131 hly selective group II p21-activated kinase (PAK) inhibitor with a novel binding mode, compound 17.

132 Signaling through p21-activated kinase (PAK) mediates several of the deleterious effects of shea

133 the activity of P21 (RAC1)-activated kinase (PAK) of group 1.

134 kinase (PI3K)/Akt, and p21-activated kinase (PAK) pathways.

135 roteins, also known as P21-activated kinase (PAK), and the mechanosensitive factor, Yes-associated pr

136 ed Cdc42 kinase (ACK), p21-activated kinase (PAK), and Wiskott-Aldrich syndrome protein (WASP).

137 its downstream target, p21-activated kinase (PAK), are regulators of insulin-stimulated glucose uptak

138 t downstream of Cdc42, p21-activated kinase (PAK), but not Par6 or WASP, may be involved in regulatin

139 phosphorylation by the p21-activated kinase (PAK), Cla4.

140 CK8, through CDC42 and p21-activated kinase (PAK), is unavailable to coordinate cytoskeletal structur

141 t scaffolding protein, p21-activated kinase (PAK), translocates to the membrane after stimulation wit

142 Rac1 and its effector p-21 activated kinase (PAK), two enzymes critically involved in actin managemen

143 nd downstream effector p21-activated kinase (PAK), we further examined Shank3 regulation of NMDARs wh

144 on with LPA as well as p21-activated kinase (PAK)-mediated lamellipodia and filopodia formation follo

145 cytoskeleton dynamics: p21-activated kinase (PAK).

146 ended on the status of p21-activated kinase (PAK).

147 in but not of synaptic p21-activated kinase (PAK).

148 id suppression of Rac1/p21-activated kinase (PAK)/protein kinase C-RAF (C-RAF)/ protein kinase MEK (M

149 Rho-kinase (ROCK) and p21-activated kinase (PAK): ROCK inhibits ULF transport, while PAK stimulates

150 hosphorylated form of p21-associated kinase (PAK), which directly inhibits MLCK.

151 The P21-activated kinases (PAK) are emerging antitumor therapeutic targets.

152 cortical activity of p21-activated kinases (PAK), which in turn controls basal body positioning in h

153 -activated serine/threonine protein kinases (PAK)-LIM domain-containing serine/threonine protein kina

154 d activity of Rac and p21-activated kinases (PAKs) and deregulation of cytoskeletal organization.

155 The p21-activated kinases (PAKs) are a family of six serine/threonine kinases that

156 The p21-activated kinases (PAKs) are immediate downstream effectors of the Rac/Cdc4

157 The type II p21-activated kinases (PAKs) are key effectors of RHO-family GTPases involved i

158 p21-activated kinases (PAKs) are serine/threonine protein kinases that serve as

159 tor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates.

160 p21-activated kinases (PAKs) become activated in cells with acquired drug resis

161 The p21-activated kinases (PAKs) play essential roles in diverse cellular processes

162 Last, p21-activated kinases (PAKs) were downregulated in SAP102 KD neurons.

163 f novel inhibitors to p21-activated kinases (PAKs), major targets of Rac1, on synaptic deterioration

164 tly reported that the p21-activated kinases (PAKs), which are activated by GTP-bound Ras-related C3 b

165 effectors, including p21-activated kinases (PAKs).

166 We substituted the major PAK sites, Ser-672 and Ser-702, with either alanine or a

167 es a potent, orally available small-molecule PAK inhibitor with significant promise for the treatment

168 l membrane-binding sites in class I myosins, PAKs and CARMIL (capping protein, Arp2/3, myosin I linke

169 docking sites for FAK-Src and GIT1/2-PIX-NCK-PAK complex), LD5, and all four carboxyl-terminal LIM do

170 -AD mice were crossed with dominant-negative PAK mice.

171 e higher virion incorporation efficiency, no PAK-2 (p21-activated kinase 2) activation, and no CD4 an

172 pathology and that therapeutic activation of PAK may exert symptomatic benefits on high brain functio

173 vasion foci, and SopE-mediated activation of PAK recruited MYO6 to actin-rich membranes.

174 n studies showed constitutive association of PAK and Akt, suggesting a possible role of PAK in Akt tr

175 eased our understanding about the biology of PAK family members.

176 In addition, the clearance of PAK (a wild-type P. aeruginosa strain) by primary AMs wa

177 re responsible for the biological effects of PAK family of kinases in cancer cells.

178 In this work, we explore the effects of PAK inhibition on RAC1(P29S) signaling in zebrafish embr

179 The efficacy of PAK inhibitors may have implications in drug discovery f

180 iting apoptosis reduced the cellular exit of PAK.

181 Importantly, disruption of the function of PAK not only uncoupled the activation of Akt from that o

182 To determine whether rapid induction of PAK phosphorylation by E(2) is mediated by nonclassical

183 expression and pharmacological inhibition of PAK both disrupt activity-dependent phosphorylation of S

184 eased in edematous tissue, and inhibition of PAK in edematous intestine improved intestinal motility.

185 helial cells via PKA-dependent inhibition of PAK.

186 lopment that can be blocked by inhibitors of PAK or MEK.

187 functional similarities, the six members of PAK family are divided into two groups with three member

188 we have summarized the complex regulation of PAK and its downstream diverse myriads of effectors, whi

189 To determine the role of PAK in AD, we first quantified PAK by immunoblotting in

190 f PAK and Akt, suggesting a possible role of PAK in Akt translocation.

191 chemistry strategies, leading to a series of PAK inhibitors that are orally active in inhibiting tumo

192 ng cofilin, the primary downstream target of PAK and a major actin depolymerizing factor, prevented S

193 ntracellularly to numbers exceeding those of PAK.

194 of concept for pan-group I, pan-group II, or PAK isoform selective inhibition has yet to be demonstra

195 e infected with P. aeruginosa strain PAO1 or PAK, which expresses ExoS, ExoT, and ExoY, but not ExoU.

196 However, inhibitors of Rac or PAK did prolong LTP's vulnerability to reversal by latru

197 ned Shank3 regulation of NMDARs when Rac1 or PAK was manipulated.

198 occluded by specific inhibitors for Rac1 or PAK, and was blocked by constitutively active Rac1 or PA

199 was blocked by constitutively active Rac1 or PAK.

200 ange factor beta-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502,

201 nly one compound, an aminopyrazole based pan-PAK inhibitor, entered clinical trials but did not progr

202 din E2-mediated GPCR activation is partially PAK-dependent and likely also involves protein kinase A,

203 r of synapses associated with phosphorylated PAK in adult hippocampal slices from wild-type, but not

204 m isolated from PAK DeltafliC or Calu-3 plus PAK DeltafliC, but it was not present in conditioned med

205 e PAK, proteinuria, the occurrence of a post-PAK kidney rejection episode, and interval between kidne

206 In our analysis, post-PAK kidney allograft loss was strongly associated with g

207 galovirus disease, and HbA1C at 6-month post-PAK) and transplant factors (time to PAK, use of inducti

208 pre-PAK and at 3-, 6-, 9-, and 12-month post-PAK, presence of proteinuria, pre- or post-PAK kidney re

209 ould be counseled regarding the risk of post-PAK renal transplant failure.

210 t-PAK, presence of proteinuria, pre- or post-PAK kidney rejection, pancreas rejection, cytomegaloviru

211 s paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design.

212 r, pre-PAK kidney rejection episode, and pre-PAK proteinuria.

213 ular filtration rate less than 45 mL/min pre-PAK, K to P interval of over 1 year, pre-PAK kidney reje

214 , glomerular filtration rate at 3 months pre-PAK and at 3-, 6-, 9-, and 12-month post-PAK, presence o

215 pre-PAK, K to P interval of over 1 year, pre-PAK kidney rejection episode, and pre-PAK proteinuria.

216 duction in PREX1 binding to PIP3 Like PREX2, PAK-mediated phosphorylation also negatively regulates P

217 Primary PAK transplants (n = 78) were compared to PRT (n=18).

218 iate-term graft survival compared to primary PAK transplantation.

219 e the role of PAK in AD, we first quantified PAK by immunoblotting in homogenates from the parietal n

220 We further demonstrate that a Rac-PAK (p21-activated kinase) signaling pathway mediates ki

221 es (LIMK1 and 2) are substrate for Cdc42/Rac-PAK and modulate actin dynamics by phosphorylating cofil

222 can be partially mitigated by increasing Rac-PAK signaling.

223 t evidence that Lis1 regulates localized Rac-PAK signaling in embryonic hair cells, probably through

224 actin polymerization, whereas the other (Rac-PAK) stabilizes the newly formed filaments.

225 results together indicate that the TRIO-RAC-PAK signaling pathway can be exploited and modulated by

226 on studies revealed that the UNC-73/TRIO-RAC-PAK signaling pathway is activated by ectopic DISC1 in C

227 eir activation by IEM-1460, included the Rac/PAK/LIM-kinase pathway that regulates spine actin dynami

228 n and can be accounted for by increased Rac1/PAK- and LIMK-dependent cofilin phosphorylation and acti

229 d the effect of PI3Kdelta inhibition on Rac1/PAK, FAK, and JNK activation.

230 Our studies suggest that Rac1/PAK is key target of PDGF-mediated PI3Kdelta signaling,

231 from apoptosis by the activation of the Rac1/PAK/AKT signaling cascade in vitro and in vivo.

232 AR hypofunction by interfering with the Rac1/PAK/cofilin/actin signaling, leading to the loss of NMDA

233 0-triggered transient activation of the Rack-PAK-LIMK pathway, and that knockdown of LIMK through siR

234 ocalized and GDP bound and failed to recruit PAK unless mutated to be constitutively active/GAP insen

235 of the prostacyclin analog iloprost reduced PAK activation and inflammatory gene expression at sites

236 ow that these two proteins together regulate PAK-LIMK-Cofilin and cyclin D1/CDK4 pathways.

237 s, synapse formation mediated by EphB/SAP102/PAK signaling in the early postnatal brain may be crucia

238 c oxide production regulates matrix-specific PAK signaling and describe a novel mechanism of nitric o

239 tient/pancreas graft survival rates for SPK, PAK, and PTA were 100%/100%, 100%/100%, and 100%/83%, re

240 patient/graft survival was 100%/100% in SPK, PAK, and PTA.

241 We conclude that pooling the results of SPK, PAK and PTA can produce potentially useful models for re

242 s in the capacity of GIT1-R283W to stimulate PAK phosphorylation in cultured hippocampal neurons.

243 In humans, insulin-stimulated PAK activation was decreased in both acute insulin-resis

244 c1 protein expression and insulin-stimulated PAK(Thr423) phosphorylation were decreased in muscles of

245 P. aeruginosa strain PAK DeltafliC (flagellin knockout) did not activate NF-k

246 ia was investigated with the invasive strain PAK and isogenic twitching motility mutants.

247 e library from the high-T3SS-producer strain PAK was introduced into the low-producer strain PAO1, an

248 anktonic cultures of P. aeruginosa K strain (PAK).

249 rotection against the flagellar type strains PAK and PA01 was maximal, but it was only marginal again

250 milar inhibitions were observed with strains PAK, PAO1, and PA14.

251 such differences in two laboratory strains, PAK and PAO1.

252 in kinase (PK)A activation, which suppresses PAK.

253 We conclude that PAK-mediated phosphorylation of PKD1 at Ser(203) trigger

254 Importantly, in vivo data indicated that PAK activity increased in edematous tissue, and inhibiti

255 Overall, our data suggest that PAK decrease is a consequence of AD neuropathology and t

256 ll of these associations were ablated by the PAK inhibitor IPA3, suggesting that PAK1 activation lies

257 targeting in lymphoma cells may involve the PAK and Akt signaling pathway, but not the mitogen-activ

258 e 1 (PAK1) and PAK3 belong to group I of the PAK family and control cell movement and division.

259 PAK4 is a member of the PAK family of serine/threonine kinases, which act as eff

260 21-activated kinase (PAK) 2, a member of the PAK family of serine/threonine protein kinases, plays an

261 n protein expression of other members of the PAK family, are present in schizophrenia.

262 nockdown phenotypes, whereas mutation of the PAK phosphorylation site is able to rescue them.

263 These data suggest that suppressing the PAK pathway might be of therapeutic benefit in this type

264 EF-PAK complex that binds GTP-Cdc42p via the PAK and promotes local Cdc42p GTP-loading via the GEF.

265 he repression of the T3SS in PAO1, while the PAK genome encodes a defective MexS, accounting for the

266 kinase activity and its interaction with the PAK-interacting exchange factor-beta (beta-Pix) are requ

267 udies have established a requirement for the PAKs in the pathogenesis of Neurofibromatosis type 2 (NF

268 These data implicate the PAKs as potential therapeutic targets.

269 at least in part, through inhibition of the PAKs.

270 to negatively regulate signaling through the PAKs and the tumor suppressive functions of Merlin are m

271 that are resistant to the combined therapy, PAKs regulate JNK and beta-catenin phosphorylation and m

272 One of these PAK inhibitors prevented progressive synaptic deteriorat

273 Moreover, this PAK inhibitor--which we call FRAX486--also rescues seizu

274 tonic inhibition of MLCK, presumably through PAK phosphorylation.

275 KA suppressed inflammatory signaling through PAK inhibition.

276 ion entailed among other factors a long K to PAK time interval; PAK could be a comparable option to S

277 bitors of BRAF but are uniquely sensitive to PAK inhibitors.

278 th post-PAK) and transplant factors (time to PAK, use of induction antibody therapy, and combinations

279 Accordingly, we found a decrease of total PAK in the cortex of 12- and 20-month-old 3xTg-AD mice,

280 A loss of total PAK, detected in the cortex of AD patients (-39% versus

281 ransplant, pancreas after kidney transplant (PAK), and pancreas transplant alone (PTA).

282 , and pancreas after kidney transplantation (PAK).

283 K], 5 pancreas after kidney transplantation [PAK], and 6 pancreas transplant alone [PTA]) between Nov

284 xposing cells to four structurally unrelated PAK inhibitors (PF-3758309, FRAX486, FRAX597, and IPA-3)

285 For SPK versus PAK recipients, there was no difference in median of len

286 sored pancreas survival rates for SPK versus PAK were 93% vs. 90%, 90% vs. 90%, and 82% versus 85%, r

287 ctive in translocation (>2 log reduction vs. PAK; P < 0.005).

288 Prominent among these were PAK-interacting exchange factor (known as Pix or RtGEF)

289 on via inhibiting MYPT1 phosphorylation when PAK activity is increased under pathologic conditions.

290 y but not in Rac-induced protrusion, whereas PAK was required for Rac-induced protrusion.

291 gnal, which sets in motion a cascade whereby PAKs phosphorylate and negatively regulate PREX2 to decr

292 To determine whether PAK dysfunction aggravates AD phenotype, 3xTg-AD mice we

293 array, revealed distinct mechanisms by which PAKs mediate resistance to BRAFi and the combined therap

294 se (PAK): ROCK inhibits ULF transport, while PAK stimulates it.

295 tion was determined by pull-down assays with PAK-agarose beads.

296 al was superior in SPK (68.8%) compared with PAK (62.5%) and PTA (16.4%).

297 , independent rescue of either motility with PAK or of Eph-ephrin binding with an EphB2 kinase mutant

298 phorylation of the aspartic acid mutant with PAK resulted in the slow phosphorylation of Thr-627, Ser

299 release, which was dramatically reduced with PAK mutants or in WT PAK-infected primary TLR5(-/-) AMs,

300 amatically reduced with PAK mutants or in WT PAK-infected primary TLR5(-/-) AMs, demonstrating the de