ライフサイエンスコーパス: kinome

1 on in the Mycobacterium tuberculosis Ser/Thr kinome.

2 ry RGCs and used it to screen the full mouse kinome.

3 ein kinase as a representative of the entire kinome.

4 ase (AMPK), which defines this branch of the kinome.

5 ti-malarial drug targets within the parasite kinome.

6 covering >80% of the human catalytic protein kinome.

7 nsive loss-of-function screen of the protein kinome.

8 racteristic of kinases in this region of the kinome.

9 at highlights areas of unmet need within the kinome.

10 esenting >50% of the predicted human protein kinome.

11 on of how inhibitors interact with the human kinome.

12 iminary in silico analysis of the sea urchin kinome.

13 NA interference (RNAi) vectors targeting the kinome.

14 understanding of the historically untargeted kinome.

15 d coverage ( approximately 80%) of the human kinome.

16 ize and activate more than half of the human kinome.

17 the appearance of kinases de novo within the kinome.

18 ificantly influence selectivity in the human kinome.

19 fy quantotypic peptides for 21% of the human kinome.

20 protein kinases, is closer to the Drosophila kinome (239) than the human kinome (518) with respect to

21 of kinase activity assays spanning the human kinome (243 kinases).

22 o the Drosophila kinome (239) than the human kinome (518) with respect to total kinase number.

23 in a regulatory manner, we performed a whole kinome (779 kinases) siRNA screen for positive or negati

24 When we compared the kinome across the six cell lines, representative of diff

25 uantitative proteomics approach, we assessed kinome activity in response to MEK inhibition in triple-

26 We applied this unique kinome-activity profiling strategy in a variety of cellu

27 edback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of i

28 Toxoplasma has in its kinome among the highest percentage of pseudokinases amo

29 A kinome analysis combined with chemical and genetic appro

30 Kinome analysis data reflected this altered host cell ph

31 ling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and

32 A global kinome analysis of CDK4-deficient mice following insulin

33 signaling intermediates identified from our kinome analysis provided partial protection in a lethal

34 Kinome analysis revealed multiple PtpA-dependent changes

35 phosphorylation events, we employed temporal kinome analysis to investigate the functional responses

36 We employed temporal kinome analysis to investigate the relative early, inter

37 ng pathway intermediates identified from our kinome analysis, also inhibited EBOV replication.

38 The large number of pseudokinases in the kinome and an increasing appreciation that they have cri

39 Kinannote produces a draft kinome and comparative analyses for a predicted proteome

40 also occur in ALL, we sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pe

41 notype 1b replicon cell line (Luc-1b) with a kinome and druggable collection of 20,779 siRNAs.

42 isms underplaying the regulation between the kinome and EMT require further elucidation to define tar

43 mily of Ser-Thr protein kinases in the human kinome and have diverse roles in broad physiological fun

44 strains representing the non-essential yeast kinome and identified a single kinase gene, ELM1, as nec

45 ng RNA (siRNA) screen targeting the cellular kinome and identified Tousled-like kinases (TLKs) as cel

46 g 734 kinase genes covering the entire mouse kinome and individually examined their effects on iPSC g

47 The tyrosine kinome and phosphatome harbor oncogenes and tumor suppre

48 ng a loss-of-function screening of the human kinome and phosphatome to identify genes suppressing tum

49 in vivo RNAi screen targeting the Drosophila kinome and phosphatome, we identify 11 kinases and phosp

50 Here we present a method to study the global kinome and phosphoproteome in tandem in a model photosyn

51 xamined nucleic acid variations in the human kinome and several known cancer-related genes in breast

52 oxoplasma and Plasmodium of their respective kinomes and phosphoproteomes.

53 Scaffold coverage varied greatly across the kinome, and many scaffolds representing compounds with d

54 ative mass spectrometry to profile proteome, kinome, and phosphoproteome changes in an established mo

55 number of cancer-associated mutations in the kinome, and the progress in developing specific small-mo

56 tegrated into inhibitor discovery across the kinome, and we outline some immediate consequences for s

57 challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the

58 The kinomes are stored in a relational database and are acce

59 Kinome array analysis demonstrated that CD28(+)CD151(+)

60 Further, the kinome array analysis identified changes in the activati

61 d by Western blotting, flow cytometry, and a kinome array protocol.

62 on that is highly conserved within the human kinome as demonstrated by our sequence analysis and stru

63 igand binding modes for the human structural kinome at scale (208 kinases, 1777 unique ligands, and t

64 selectivity over group I PAKs, and the broad kinome, based on unique flexibility of this lipophilic p

65 demonstrate that Cdc37 has a general role in kinome biogenesis.

66 ed by wrapping differences across its target kinome can selectively direct its impact toward a specif

67 han 500 protein kinases comprising the human kinome catalyze hundreds of thousands of phosphorylation

68 uantitative phosphoproteomics with mammalian kinome cDNA library screen.

69 ed kinase inhibition can induce compensatory kinome changes, rendering single therapeutic agents inef

70 Thus, the sea urchin kinome combines the simplicity of a non-duplicated genom

71 The human protein kinome comprises 535 proteins that, with the exception o

72 The human kinome comprises over 800 individual kinases.

73 The results show that the sea urchin kinome, consisting of 353 protein kinases, is closer to

74 The kinome consists of 518 kinases, and every active protein

75 everal classes of signaling molecules, their kinomes contain a large and diverse set of protein kinas

76 uggests that other pseudokinases (10% of the kinome) could also be catalytically active.

77 inase expression and activation have limited kinome coverage.

78 -protein interaction networks generated from kinome data could further be used to guide targeted gene

79 analysis and functional network analysis of kinome data revealed that transforming growth factor (TG

80 Upregulation of TGF-beta signaling in the kinome data sets correlated with the upregulation of TGF

81 Mining of the kinome database revealed that a subset of some 46 kinase

82 he complement of Drosophila protein kinases (kinome) for cell cycle functions after gene silencing by

83 is of all known sequences in the A. thaliana kinome found that alphaC helix disorder may be a common

84 Approximately one-third of the Drosophila kinome has been ascribed some cell-cycle function.

85 ted Tyr and Ser/Thr kinases, over 85% of the kinome has been identified to be dysregulated in at leas

86 Structural coverage of the human kinome has been steadily increasing over time.

87 The strategy of 'drugging the cancer kinome' has led to the successful development and regula

88 e kinase complement of the human genome, the kinome, has provided an excellent starting point for und

89 essential functions for the malaria parasite kinome have been reported, the roles of most protein pho

90 Recent analysis of the Plasmodium falciparum kinome identified several kinases that are entirely uniq

91 ification and comparison with model organism kinomes identified orthologous groups and highlighted ex

92 A recent analysis of the tyrosine kinome in colorectal cancer identified c-fes as one of o

93 ly the arsenite-induced alteration of global kinome in human cells.

94 cell growth, transcriptome, metabolome, and kinome in response to paracrine signals emerging from ir

95 Analysis of the platelet kinome in the context of the kinase phylogenetic backgro

96 constituting an extensive and diverse sugar kinome in the thermophilic bacterium Thermotoga maritima

97 e protein kinases ( approximately 50% of the kinome) in a cdc37 mutant strain showed that 51 had decr

98 erved only in 8 of the >90 PTKs in the human kinome, including 3 of the 10 Src family kinases and all

99 WNK kinases are unique members of the human kinome, intimately involved in maintaining electrolyte b

100 s (approximately 70% of mammalian structural kinome) into accurate and specific models of their type-

101 Thus, about half of the human kinome is currently covered with active small molecules.

102 roducing hypotheses that can explain how the kinome is involved in the maintenance of different cellu

103 risingly similar to humans, since the urchin kinome is missing only 4 of 186 human subfamilies, while

104 The distribution of inhibitors across the kinome is uneven.

105 tivity of Cdc37 could dramatically alter the kinome, leading to profound changes in the tau phosphory

106 e delivery and/or expression by performing a kinome-level screen in which, we identified small-molecu

107 We constructed a SILAC-compatible kinome library for scheduled multiple-reaction monitorin

108 er cells with a lentivirus short hairpin RNA kinome library.

109 itative assessment of perturbation in global kinome may provide crucial knowledge for elucidating the

110 quantitative analysis of the perturbation of kinome of GM00637 human skin fibroblast cells induced by

111 omprehensively the alterations of the global kinome of HEK293T human embryonic kidney cells upon trea

112 his study provides a global insight into the kinome of S. haematobium and should assist the repurposi

113 In this context, we defined here the kinome of S. haematobium using a refined bioinformatic p

114 The kinome of the human malaria parasite Plasmodium falcipar

115 ned the full protein kinase (PK) complement (kinome) of mouse.

116 se in coverage of the enriched Chlamydomonas kinome over coverage found with no enrichment.

117 For larger "kinome" panels, the partition index allows assessment of

118 king of altered kinases generated from these kinome profile data predicted PIM-1 kinase as a key swit

119 Kinome profiling and cellular studies demonstrate that,

120 latent HIV-1 integration event and position kinome profiling as a research tool to reveal novel mole

121 hanism of sorafenib activity through in situ kinome profiling identified the mitogen-activated protei

122 -throughput, SILAC-compatible, and MRM-based kinome profiling method and demonstrated that the method

123 Together, our targeted kinome profiling method offers a powerful resource for e

124 The improved kinome profiling methods described here represent an eff

125 Kinome profiling revealed 5-IT to be a potent and select

126 Moreover, kinome profiling uncovers disruption of multiple signal

127 Kinome profiling versus more than 300 kinases in vitro a

128 The KAYAK (Kinase ActivitY Assay for Kinome profiling) assay measures the phosphorylation rat

129 ellular phosphorylation events (often called kinome profiling).

130 dvanced analysis tools are yet available for kinome profiling.

131 as compared to classical analysis tools for kinome profiling.

132 Unbiased transcriptional and kinome reprogramming analyses from selected treatment ti

133 but lost its direct antitumor effects due to kinome reprogramming, which resulted in suppression of p

134 ion of proteasomal c-Myc degradation blocked kinome reprogramming.

135 relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes.

136 The average sensitivity and precision for kinome retrieval from the test species are 94.4 and 96.8

137 nalysis of the mutation catalog in the human kinome revealed the presence of cancer-associated mutati

138 c targets, we performed an unbiased tyrosine kinome RNA interference screen in primary cell cultures

139 From a human kinome RNAi screen, we have identified Lats2 kinase as a

140 therapeutic efficacy of RITs, we conducted a kinome RNAi sensitization screen, which identified disco

141 m publicly available inhibitors of the human kinome, scaffolds and cyclic skeletons were systematical

142 ith protein tyrosine kinases is conducted on kinome scale by using evolutionary analysis and fingerpr

143 Further kinome-scale siRNA screening demonstrated that SRC MEK5

144 Using a kinome screen and a systems biology approach, we identif

145 An RNAi-based kinome screen revealed that LYN is required for growth o

146 e of intracellular signaling, we performed a kinome screen using a label-free assay and found that me

147 Here using an unbiased siRNA kinome screen, we identify and validate casein kinase 1a

148 creen the P. berghei kinome, using published kinome screens for comparison.

149 In Ambit kinome screens, cell growth inhibition studies, and surr

150 Furthermore, we developed a kinome selective irreversible inhibitor 45a with an IC50

151 emphasize the outstanding properties of the kinome-selective JAK inhibitor CP-690550, as well as the

152 21i (AC081), two structurally novel, potent, kinome-selective pan-Aurora inhibitors.

153 Development of a series of highly kinome-selective spleen tyrosine kinase (Syk) inhibitors

154 ora A inhibitor (IC50 = 2 nM) with very high kinome selectivity for Aurora kinases.

155 tent LRRK2 inhibitors, focusing on improving kinome selectivity using a surrogate crystallography app

156 razines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versu

157 f kinase therapeutics with high efficacy and kinome selectivity, thus avoiding problems observed with

158 Data from this first siRNA-kinome sensitizer screen suggests that inhibiting WEE1 i

159 Cancer kinome sequencing studies have identified several protei

160 Assessment of the phospho-kinome showed decreased phosphorylation of pathways invo

161 B4 mutations can induce broad changes in the kinome signature of lung cancer cells.

162 Screening libraries of kinome siRNA and small molecules, we defined PLK1 as an

163 In accordance with the chemical screen, kinome small interfering RNA high throughput screens ide

164 ucture-binding relationships in the tyrosine kinome space in which evolutionary analysis of the kinas

165 mined by their phylogenetic proximity in the kinome space or differences in the interactions with the

166 e interrogation of all elements of the human kinome supporting EGF-dependent signaling.

167 architecture of the M. tuberculosis Ser/Thr kinome that could enable horizontal signal spreading.

168 focusing on mutations in the kinase genome (kinome) that lead to tumorigenesis.

169 ein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for descr

170 se of high-throughput screening of the yeast kinome to facilitate the major task of identifying human

171 y, we performed an siRNA-based screen of the kinome to identify genetic regulators of PGRN levels in

172 ved models are evenly distributed across the kinome tree, allowing reliable profiling prediction for

173 rotein and lipid kinases, leaving 70% of the kinome untapped.

174 kinase complement of the human genome (the "kinome") using public and proprietary genomic, complemen

175 of this resource, we rescreen the P. berghei kinome, using published kinome screens for comparison.

176 Relying on extensive human kinome vetting, we show that (R)-3 is the most potent an

177 NAi) screen targeting 542 genes of the human kinome was used to discover regulators of RNAi.

178 Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1

179 Through RNAi screening of the kinome, we have identified Misshapen (Msn) and the mamma

180 , by conducting a shRNA screen targeting the kinome, we identified PIM1, a non-essential serine-threo

181 Through a systematic evaluation of the kinome, we identified Pro455 and Asn457 in the Syk ATP b

182 ove our understanding of HIF-1 regulation by kinome, we screened a kinase-specific small interference

183 ymatic assays, chemical proteomic profiling, kinome-wide activity surveys and MTH1 co-crystal structu

184 Finally, we present the kinome-wide analysis of mRNA expression dynamics induced

185 Our calculations predict a kinome-wide conformational plasticity, and indicate the

186 e presented approach opens possibilities for kinome-wide discovery of specific molecules targeting in

187 l of multiple endocrine neoplasia type 2 and kinome-wide drug profiling, here we identify that AD57 r

188 hese agents, we have undertaken a systematic kinome-wide effort to profile their selectivity and pote

189 Using a chemogenomics approach marrying kinome-wide inhibitory profiles of a compound library wi

190 We further reported a kinome-wide landscape of pharmacogenomic interactions by

191 computational oncoproteomics approach, named kinome-wide network module for cancer pharmacogenomics (

192 from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library.

193 In turn, through a kinome-wide phosphoproteomic and MS study, we demonstrat

194 tudies establish the feasibility of tyrosine kinome-wide phosphorylation profiling and point to SRC a

195 Combining kinase-focused chemistry, kinome-wide profiling and Drosophila genetics provides a

196 e, we desired to increase the throughput for kinome-wide profiling.

197 A kinome-wide reverse genetics strategy identified 36 para

198 mbine global phospho-proteomic analysis with kinome-wide reverse genetics to assess the importance of

199 l components of this pathway, we performed a kinome-wide RNA interference (RNAi) screen in Drosophila

200 A kinome-wide RNA interference screen was used to identify

201 to gammaherpesvirus through two independent kinome-wide RNA interference screens.

202 A recent kinome-wide RNAi screen with 176 individual bloodstream

203 Using unbiased kinome-wide RNAi screening followed by thorough validati

204 Here, we report a kinome-wide RNAi-based analysis to identify kinases that

205 The kinome-wide screen demonstrated a strong inverse correla

206 ical properties and notable selectivity in a kinome-wide screen.

207 Kinome-wide screening would have the advantage of provid

208 These kinome-wide screens, performed within a day on a small c

209 s illustrate for the first time the use of a kinome-wide selective radioactive chemical probe for end

210 Kinome-wide selectivity profiling of the library resulte

211 Kinome-wide sequence mining revealed rare presentation o

212 We performed a kinome-wide siRNA screen and identified 70 kinases alter

213 Here, a comprehensive kinome-wide siRNA screen in a human HeLa cell-based mode

214 A kinome-wide siRNA screen showed that the insulin recepto

215 In this study, we used a kinome-wide siRNA screen to identify kinases that, when

216 A kinome-wide siRNA screen using a library targeting 720 k

217 as were other protein kinases identified by kinome-wide siRNA screening and a genetic gain-of-functi

218 d a functional kinomics approach including a kinome-wide siRNA-phosphoproteomic screen, a high-conten

219 We therefore conducted a kinome-wide small interfering RNA (siRNA) lethality stud

220 tly label a broad swath of the intracellular kinome with high efficiency.

221 cted a siRNA screening targeted to the human kinome with the aim of discovering new EMT effectors.

222 selection of kinases from each branch of the kinome, with and without known substrates, highlighting