ライフサイエンスコーパス: Csk

1 Csk and SFKs share a modular design with the kinase doma

2 Csk and Src are two protein tyrosine kinases that share

3 Csk and Src protein tyrosine kinases are structurally ho

4 Csk bound to and phosphorylated PECAM-1 more efficiently

5 Csk cannot phosphorylate substrates that lack this docki

6 Csk catalytic domain is inactive and is positively regul

7 Csk colocalization with G3BP occurred in this "parasynap

8 Csk knock-out mice died at early stages of embryogenesis

9 Csk knockdown induced VE-cadherin phosphorylation at sit

10 Csk migrates to lipid raft domains, where it decreases p

11 Csk plays an important role, not only in basal signaling

12 Csk was translocated to the membrane where it down-regul

13 Csk, in turn, keeps integrin-associated c-Src in an inac

14 Csk, the physiological inhibitor of cSrc, was present in

15 ortance of this difference by constructing a Csk variant with a longer SH2 CD loop to mimic the flexi

16 signaling, we generated mice that express a Csk variant sensitive to an analog of the common kinase

17 We have identified a Csk-like kinase (CoCsk) in the genome of C. owczarzaki.

18 tively interacts with its substrate Lck in a Csk-dependent manner.

19 gest that tyrosine-phosphorylated JAM-A is a Csk-binding protein and functions as an endogenous inhib

20 ntaining proteins to the SH2 domain activate Csk.

21 g Csk activity, and their mutation activates Csk, but makes Csk less sensitive to activation by the S

22 the Csk catalytic domain to obtain an active Csk catalytic domain.

23 H-terminal Src kinase (Csk) and the adaptor, Csk-binding protein.

24 Although Csk is known as a negative regulator of Src kinases, the

25 Importantly, Src activation and Csk down-regulation are also observed in colon cancer ce

26 However, both c-Src activity and Csk localization at the membrane were similar between Ca

27 c-Src forms a complex with alphaIIbbeta3 and Csk, which phosphorylates c-Src tyrosine 529 to maintain

28 Btk and Csk function downstream of phosphatidylinositol 3-kinase

29 isrupting the association of VE-cadherin and Csk through the reconstitution of Csk binding-defective

30 we show that relative titration of CD45 and Csk expression reveals distinct regulation of basal and

31 CD45 and Csk provide positive and negative regulatory control of

32 uman colon cancer cell lines, HT29 cells and Csk shRNA-transfected HT29 cells that exhibit different

33 Chemical and Csk-based genetic inhibitor treatments revealed that SFK

34 rosine kinases contains two members: Csk and Csk homologous kinase (Chk).

35 he library method to kinases Pim1, MKK6, and Csk revealed that Pim1 and Csk are highly active toward

36 s Pim1, MKK6, and Csk revealed that Pim1 and Csk are highly active toward peptide substrates and reco

37 osis transmembrane conductance regulator and Csk-binding protein were also found to act as transferab

38 control of SFK functions, respectively, and Csk is constitutively bound to the transmembrane adapter

39 re was pronounced colocalization of SFKs and Csk at the site of TCR triggering, whereas in Ag-experie

40 dherin was basally associated with c-Src and Csk (C-terminal Src kinase), a negative regulator of Src

41 For example, in choanoflagellates, Src and Csk are both active, but the negative regulatory mechani

42 Although Src and Csk orthologs are present across holozoan organisms, inc

43 owth assays to characterize holozoan Src and Csk orthologs.

44 ese results, together with available Src and Csk tertiary structures, reveal an important structural

45 Strikingly, Src64 and Csk function in the germline to control packaging, not i

46 ment of Csk to the membrane and that another Csk adaptor, yet to be discovered, compensates for the l

47 reciable differences in domain architecture, Csk from Corallochytrium limacisporum, a highly diverged

48 ssion level of the other membrane-associated Csk adaptor to maintain SFK inhibition.

49 Whereas SFKs are membrane-associated, Csk is a cytoplasmic protein and therefore requires memb

50 he variant associated with T1D does not bind Csk.

51 Although both Csk and MAP kinases used docking sites for substrate rec

52 First, both Csk and Src phosphorylate Src as a common substrate, but

53 These results uncover novel roles for both Csk and Src64 in a dynamic event that involves adhesion,

54 TRAF3 resulted in increased amounts of both Csk and PTPN22 in T cell membrane fractions and decrease

55 ted to choanoflagellates, Src is active, but Csk is apparently inactive.

56 lation of the N-terminal ITIM of Siglec-9 by Csk is enhanced by the prior phosphorylation of its C-te

57 ation loop (which increases activity) and by Csk-mediated phosphorylation of the C-terminal tail (whi

58 c family tyrosine kinase (SFK) inhibition by Csk.

59 ne 505, which was normally phosphorylated by Csk and dephosphorylated by CD45 in the mutants.

60 In contrast to the role played by Csk in the regulation of Src64 activity during packaging

61 kinases known to be negatively regulated by Csk were then examined; knock down of one of these kinas

62 s suggest that negative regulation of Src by Csk is more ancient than previously thought and that it

63 sphorylation of their C-terminal tyrosine by Csk.

64 high GM3 level by exogenous addition caused Csk translocation into glycosynapse, with subsequent inh

65 kinase), and its transmembrane adaptor, Cbp (Csk-binding protein).

66 es revealed that translocation of Lyn, CD45, Csk, and c-Cbl led to increased recruitment and retentio

67 ial microenvironment: Src-transformed cells (Csk-deficient) were influenced by their immediate normal

68 triggering, whereas in Ag-experienced cells, Csk displayed a bipolar distribution with a proportion o

69 wth-inhibited cells was caused by coexisting Csk in WI38 GEM.

70 By contrast, Csk titration regulates basal but not inducible signalin

71 e Csk regulator PAG/Cbp, thereby controlling Csk access to SFKs.

72 on with other Csk orthologs, Corallochytrium Csk displays broad substrate specificity and inhibits Sr

73 during positive selection and to counteract Csk during basal TCR signaling.

74 we utilized a mouse expressing mutated Csk (Csk(AS)) whose catalytic activity is specifically and ra

75 The genetic deletion of Csk (Csk(-)(/)(-)) in mouse embryonic fibroblasts blocked the

76 Thus, recruitment of cytosolic Csk to the membrane-associated SFKs is crucial for its r

77 Reduction in d-Csk expression and the consequent activation of Src are

78 The Drosophila C-terminal Src kinase (d-Csk) is a genetic modifier of warts (wts), a tumor-suppr

79 rity in the loss-of-function phenotypes of d-Csk and wts, we have investigated the interactions of d-

80 , we have investigated the interactions of d-Csk with the Hippo pathway.

81 Previous studies show that d-Csk regulates cell proliferation and tissue size during

82 multiple lines of evidence suggesting that d-Csk regulates growth via the Hippo signaling pathway.

83 of Src kinase by overexpressing kinase-dead Csk failed to reverse the inhibitory effect of Pyk2(Y402

84 SH2 domain whose mutation severely decreases Csk catalytic activity without affecting the SH2 ligand-

85 PTP-1B is required for fibrinogen-dependent Csk dissociation from alphaIIbbeta3, dephosphorylation o

86 Protein (dASPP) as a regulator of Drosophila Csk (dCsk) activity.

87 ow that PSTPIP2 binds the inhibitory enzymes Csk and SHIP1.

88 rodomains (PAG), is the membrane adaptor for Csk.

89 A similar mechanism was confirmed for Csk recognition of another Src family kinase, Yes.

90 First, the SH3-SH2 linker is crucial for Csk activation.

91 a basis for different cellular functions for Csk and Chk.

92 he regulatory domains that are important for Csk activation.

93 ng-based substrate recognition mechanism for Csk.

94 the regulatory region, but not required for Csk activation triggered by a phosphopeptide binding to

95 Our data demonstrate a critical role for Csk in cell migration.

96 and proteins, further supporting a role for Csk in HCV replication.

97 we identified a new Src-independent role for Csk in the control of Gliotactin, a key tricellular junc

98 of six proteins, as follows: BCR, Lyn, Fyn, Csk, PAG1, and Syk, a cytosolic protein tyrosine kinase

99 To investigate how Csk activity regulates T cell antigen receptor (TCR) sig

100 To understand how Csk recognizes Src, the chemical/physical events that mo

101 ase are fast and that a structural change in Csk participates in limiting the catalytic cycle.

102 ic function and interdomain communication in Csk.

103 Interestingly, the preferential decrease in Csk protein synthesis is a consequence of increased eIF2

104 s to recognize substrates is destabilized in Csk by a deletion in the activation loop.

105 largely controlled by one residue, Glu127 in Csk, Ile167 in Chk, and Lys200 in Src.

106 ty of Csk, but were not directly involved in Csk recognition of its physiological substrate, Src.

107 talytic domain, but the equivalent motifs in Csk directly interact with the regulatory domains that a

108 negative regulatory mechanism is present in Csk and Src proteins from C. owczarzaki and the choanofl

109 evated PRL3 expression causes a reduction in Csk level, leading to Src activation.

110 lexibility in several polypeptide regions in Csk, tyrosine substitution increases flexibility, and al

111 Increased Csk suppresses the Gliotactin overexpression phenotypes

112 ll-atom structure-based simulations indicate Csk occupies two free energy basins.

113 ine and phenylalanine hydroxamates inhibited Csk activity only in the presence of Co(2+).

114 Instead, Csk becomes associated with an approximately 72-kDa tyro

115 here also exists in these cells an intrinsic Csk-dependent cellular defense mechanism aimed at impair

116 C proteins, ezrin binding protein of 50 kDa, Csk binding protein, and the p85 subunit of PI3K was par

117 s thought to be due to the homologous kinase Csk that compensates for Matk/CHK.

118 ibits its association with inhibitory kinase Csk, allowing autophosphorylation of Src at residue tyr4

119 expression of the negative regulatory kinase Csk suppressed SFK activity and reversed the growth-inhi

120 ch lacks the negative regulatory tail kinase Csk, wild-type Hck was more strongly activated in the pr

121 (LYP), which forms a complex with the kinase Csk and is a critical negative regulator of signaling th

122 To understand how the kinase Csk, a negative regulator of SFKs, controls the basal st

123 Tyrosine kinase Csk is essential for mouse embryonic development.

124 cruits the cytosolic protein tyrosine kinase Csk to the plasma membrane, where it acts to decrease th

125 tyrosine by the nonreceptor tyrosine kinase Csk.

126 report that the nonreceptor-tyrosine-kinase Csk is an essential component of the intracellular modul

127 ylation event include C-terminal Src kinase (Csk) and Bruton's tyrosine kinase (Btk).

128 wn inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22).

129 tive regulation by COOH-terminal Src kinase (Csk) and the adaptor, Csk-binding protein.

130 We identified C-terminal Src kinase (Csk) as a tyrosine kinase responsible for regulating Gli

131 presence of the carboxy-terminal Src kinase (Csk) at the cell membrane.

132 cooperative roles of C-terminal Src kinase (Csk) binding protein (Cbp) and Caveolin-1 (Cav-1) in the

133 C-terminal Src kinase (Csk) binds to tyrosine phosphorylated JAM-A through its

134 C-terminal Src kinase (Csk) contains a catalytic domain and a regulatory region

135 The C-terminal Src kinase (Csk) contains a catalytic domain and the regulatory SH3

136 f Src64 by Drosophila C-terminal-Src Kinase (Csk) contributes to the packaging of germline cysts by o

137 C-terminal Src kinase (Csk) encodes a critical negative regulator of Src family

138 The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two mem

139 C-terminal Src kinase (Csk) is a multidomain tyrosine kinase that is up-regulat

140 The C-terminal Src kinase (Csk) phosphorylates and down-regulates Src family tyrosi

141 C-terminal Src kinase (Csk) phosphorylates and down-regulates the Src family ty

142 C-terminal Src kinase (Csk) specifically phosphorylates Src family kinases on a

143 cells mediated by COOH-terminal Src kinase (Csk) that negatively regulates Pseudomonas invasion.

144 ed inhibitors against C-terminal Src kinase (Csk), a protein tyrosine kinase.

145 tion of Lyn, CD45, COOH-terminal Src kinase (Csk), and c-Cbl were studied by Western blotting, confoc

146 The C-terminal Src kinase (Csk), the primary negative regulator of Src-family kinas

147 which is catalyzed by C-terminal Src Kinase (Csk).

148 C-terminal region by C-terminal Src kinase (Csk).

149 il by another kinase, C-terminal Src kinase (Csk).

150 ic activity in the COOH-terminal Src kinase (Csk).

151 ncipal control of the C-terminal Src Kinase (Csk).

152 r negative regulator, C-terminal Src kinase (Csk).

153 een the SH3 domain of C-terminal Src kinase (Csk-SH3) and a proline-rich peptide from proline-enriche

154 The SH2 domain of the C-terminal Src kinase [Csk] contains a unique disulfide bond that is not presen

155 down-regulated by the C-terminal Src kinase, Csk.

156 The c-Src tyrosine kinase, Csk, physically interacts with the intracellular phospha

157 Prior studies on protein tyrosine kinases Csk and Src revealed the potential for chemical rescue o

158 rence RNAs specific for three human kinases, Csk, Jak1, and Vrk1, were identified that reproducibly r

159 The kinase activity of full-length Csk decreases by an order of magnitude upon formation of

160 The Csk-binding protein (Cbp) localizes Csk close to its substrates at the plasma membrane, and

161 This suggests that the Lyp-Csk complex increases susceptibility to lupus at multipl

162 ts in the LYP-R620W variation within the LYP-Csk interaction motif.

163 and their mutation activates Csk, but makes Csk less sensitive to activation by the SH2 ligand.

164 dressed the mechanism by which PRL3 mediates Csk down-regulation.

165 demonstrate that the Drosophila melanogaster Csk ortholog, dCsk, functions as a tumor suppressor: dCs

166 otein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk).

167 with glycosphingolipid-enriched microdomains/Csk binding protein (PAG/Cbp), an adaptor protein that c

168 However, recent structural studies of mutant Csk in the presence of an inhibitor indicate that the en

169 ling, we utilized a mouse expressing mutated Csk (Csk(AS)) whose catalytic activity is specifically a

170 However, dominant negative Csk expression was unable to induce changes in the monol

171 f SFK by overexpression of dominant negative Csk induced VE-cadherin phosphorylation at tyrosines 658

172 and SFKs by expression of dominant negative Csk, expression of constitutively active Src, or knockdo

173 G3BP reduced the ability of Csk to phosphorylate Lck at Y505 by decreasing the amoun

174 but proceed constitutively in the absence of Csk.

175 n mediating a ligand-triggered activation of Csk because their mutation severely reduces Csk activati

176 se residues likely mediate SH2 activation of Csk regardless of SH2-ligand interaction.

177 mediating SH2 ligand-triggered activation of Csk.

178 o demonstrate that the catalytic activity of Csk is required for its modulatory function.

179 crucial in maintaining the full activity of Csk, but were not directly involved in Csk recognition o

180 late Lck at Y505 by decreasing the amount of Csk in lipid rafts.

181 r signaling and acts to reduce the amount of Csk in the immune synapse.

182 tion then confirmed increased association of Csk with phosphomimicking Cav-1.

183 osphorylation of Src and the conformation of Csk were investigated in the presence of a high-affinity

184 nsembles of distinct global conformations of Csk: a compact structure and an extended structure.

185 n the gene-specific translational control of Csk expression.

186 The genetic deletion of Csk (Csk(-)(/)(-)) in mouse embryonic fibroblasts blocke

187 Furthermore, deletion of Csk did not interfere with Rac activation and lamellipod

188 activation by blocking the disassociation of Csk from VE-cadherin.

189 n the tyrosine, allowing the dissociation of Csk from the integrin complex, and thus facilitating out

190 ated with Csk, promoting the dissociation of Csk from the plasma membrane.

191 The SH2 domain of Csk is an essential component for the down-regulation of

192 The isolated catalytic domain of Csk is intrinsically inactive and is activated by intera

193 A unique feature of the SH2 domain of Csk is the tight turn in place of the canonical CD loop

194 all Cbp-derived peptide to the SH2 domain of Csk modifies these motions, enhancing Src recognition.

195 e of a complex between the kinase domains of Csk and c-Src at 2.9 A resolution, revealing that intera

196 gest that the Src homology (SH) 2 domains of Csk and Chk may bind to different phosphoproteins, which

197 ween the regulatory and catalytic domains of Csk.

198 ive regulator of Src kinases, the effects of Csk on Gliotactin are independent of Src and likely occu

199 ADP can shift the conformational ensemble of Csk in solution using a combination of small angle x-ray

200 Re-expression of Csk in these Csk-deficient cells rescued the migratory p

201 her share some of the regulatory features of Csk instead.

202 are similar to that for a truncated form of Csk lacking the SH2 domain, suggesting that a single mut

203 e domain generates further extended forms of Csk that may have relevance for kinase scaffolding and S

204 Thus, the function of Csk as a negative regulator of Src family kinases appear

205 Inhibition of Csk(AS) during TCR stimulation led to stronger and more

206 Inhibition of Csk(AS) enhanced activation by weak but strictly cognate

207 Inhibition of Csk(AS) in thymocytes, without engagement of the TCR, in

208 con cells with a small molecule inhibitor of Csk also resulted in a significant reduction in HCV RNA

209 ustering using a small-molecule inhibitor of Csk, which increased SFK activation and produced robust

210 nd evaluated as metal-mediated inhibitors of Csk, leading to improved inhibition and a better underst

211 this study, we generated chimeric kinases of Csk and Src by switching the C-terminal lobes of their c

212 f constitutively active Src, or knockdown of Csk.

213 Loss of Csk causes Gliotactin to spread away from the TCJ.

214 The Lyn-dependent phosphorylation of Csk-binding protein, which negatively regulates Fyn acti

215 d each SFK with HIV-1 Nef in the presence of Csk.

216 dherin and Csk through the reconstitution of Csk binding-defective mutant of VE-cadherin also diminis

217 at Cbp is dispensable for the recruitment of Csk to the membrane and that another Csk adaptor, yet to

218 Moreover, recruitment of Csk to the specialized membrane compartment of "lipid ra

219 studies demonstrated that the regulation of Csk activity is linked to conformational changes in the

220 protein synthesis, rather than regulation of Csk mRNA levels or protein turnover.

221 ed to be indirect through down-regulation of Csk, a negative regulator of Src.

222 es Src activation through down-regulation of Csk, a negative regulator of Src.

223 play an important role in the regulation of Csk.

224 ell antigen receptor results in a removal of Csk from the lipid raft-associated transmembrane protein

225 Despite the fundamental role of Csk in controlling cell growth and differentiation, it i

226 of PRL3 in tumor metastasis and the role of Csk in controlling Src activity, we addressed the mechan

227 l of c-Src at the edge of the active site of Csk.

228 tant for maintaining the active structure of Csk by the presence of the regulatory region, but not re

229 Although the X-ray structure of Csk suggests the enzyme is compact, X-ray scattering stu

230 This report extended previous studies of Csk domain-domain communication, and provided a foundati

231 Crystallographic studies of Csk found an unusual arrangement of the SH2 and SH3 regu

232 family kinases are the only known targets of Csk.

233 ough its catalytic loop is more like that of Csk.

234 Titration of Csk inhibition revealed that a very small increase in SF

235 des functional insights into the topology of Csk family of protein tyrosine kinases.

236 PRL3 is shown to exert a negative effect on Csk protein synthesis, rather than regulation of Csk mRN

237 or), PP2 (Src-specific kinase inhibitor), or Csk (cellular negative regulator for Src), as well as do

238 o show that bistability can arise in Lyn- or Csk-deficient cells.

239 However, in comparison with other Csk orthologs, Corallochytrium Csk displays broad substr

240 gulation of Src64 activity during packaging, Csk is dispensable for ring canal growth control, indica

241 The kinase-phosphatase pair Csk and CD45 reciprocally regulate phosphorylation of th

242 cells, in the context of its binding partner Csk, unmasks the risk allele as a hypomorph.

243 bstrate and phosphatase SHP-1 as a potential Csk substrate.

244 n analog of the common kinase inhibitor PP1 (Csk(AS)).

245 family kinase negative regulatory proteins, Csk (C-terminal Src kinase), and its transmembrane adapt

246 PDGF-elicited c-myc induction by recruiting Csk to active Src kinases, whereupon their activities an

247 tively regulate c-Src activity by recruiting Csk to the membrane where it phosphorylates c-Src inhibi

248 Thus, JAM-A recruits Csk to the integrin-c-Src complex in resting platelets.

249 JAM-A recruits Csk to the integrin-c-Src complex, where Csk negatively

250 Reduced Csk synthesis also occurs in response to cellular stress

251 of a catalytic tyrosine; and Fyn, by reduced Csk phosphorylation of the inhibitory COOH-terminal tyro

252 Csk because their mutation severely reduces Csk activation by the SH2 domain ligand.

253 l line (CSK-) lacking the negative regulator Csk gene of the Src kinase family.

254 The roles of Src and its negative regulator Csk have been extensively studied, although results have

255 d, a single point mutation of E127K rendered Csk responsive to activation by a Src SH2 domain ligand.

256 Second, Csk and Src represent two general regulatory strategies

257 The selected Csk substrates show strong sequence covariance and fall

258 A member of this family, SLP65/SLP76, Csk-interacting membrane protein (SCIMP), recruits a com

259 TP-1B recruitment to the alphaIIbbeta3-c-Src-Csk complex in a manner that is dependent on c-Src and s

260 to the same degree seen in the mammalian Src/Csk pair.

261 VEGF stimulated Csk release from VE-cadherin by recruiting the protein t

262 Type II residues are involved in suppressing Csk activity, and their mutation activates Csk, but make

263 Our data demonstrate that Csk is involved in the control of cGMP levels and that m

264 We have previously determined that Csk recognizes Src using a substrate-docking site away f

265 e, providing the first in vivo evidence that Csk regulates SFKs during development through phosphoryl

266 Here we report that Csk deficiency in mouse embryonic fibroblast cells block

267 n contrast to previous studies, we show that Csk from the filasterean Capsaspora owczarzaki is active

268 ulation of the HCV replicon, suggesting that Csk mediates its effect on HCV replication through Fyn.

269 It suggests that Csk adopts a broad ensemble of conformations in solution

270 The Csk tyrosine kinase negatively regulates the Src family

271 The Csk-binding protein (Cbp) localizes Csk close to its sub

272 ologic inhibitor of Src kinase activity, the Csk homologous kinase (CHK), expressed as a mammary tiss

273 ween the docking determinants of Src and the Csk substrate-docking site for this recognition.

274 striking functional differences between the Csk and Chk SH2 domains and revealed functional similari

275 ocking determinants in Src recognized by the Csk substrate-docking site and demonstrated an interacti

276 utating Lys200 in Src SH2 domain to Glu (the Csk counterpart) resulted in loss of Src SH2 function.

277 the apparent phosphoryl transfer rate in the Csk active site, a phenomenon detected in rapid quench f

278 Mutating these residues in the Csk or Chk SH2 domain to the Src counterpart resulted in

279 ion by regulating the phosphorylation of the Csk regulator PAG/Cbp, thereby controlling Csk access to

280 e, we compared the binding properties of the Csk, Chk, and Src SH2 domains and investigated the struc

281 ganisms, including animals and protists, the Csk-Src negative regulatory mechanism appears to have ev

282 tro and transgenic models suggested that the Csk-binding protein (Cbp), also known as phosphoprotein

283 Capsaspora owczarzaki is active and that the Csk-Src negative regulatory mechanism is present in Csk

284 The Src motifs can be grafted to the Csk catalytic domain to obtain an active Csk catalytic d

285 linker, provide a dynamic balance within the Csk framework that is ideal for efficient phosphoryl tra

286 Re-expression of Csk in these Csk-deficient cells rescued the migratory phenotype.

287 ibiting the c-Src activity, possibly through Csk translocation.

288 Thus, Csk has a critical role in preventing TCR signaling.

289 c pathway activity, most likely by titrating Csk activity away from endogenous Src.

290 its Csk to the integrin-c-Src complex, where Csk negatively regulates c-Src activation, thereby suppr

291 ox because of this cysteine residue, whereas Csk, a PTK that lacks a cysteine residue at the correspo

292 data are consistent with a mechanism whereby Csk achieves a low K(m) for the substrate Src, not by st

293 TRAF3 associated with Csk, promoting the dissociation of Csk from the plasma m

294 in-1 were phosphorylated and associated with Csk.

295 exhibits a greatly reduced interaction with Csk and is a gain-of-function inhibitor of signaling.

296 ons and decreased association of PTPN22 with Csk.

297 Matk/CHK is not functionally redundant with Csk, and that this tyrosine kinase plays an important ro

298 monstration that replicon cells treated with Csk inhibitor contained lower levels of the phosphorylat

299 We find wt-Csk frequently occupies an extended conformation where t

300 To investigate whether wt-Csk may also access open conformations we applied small