ライフサイエンスコーパス: SH2 domain

1 an equivalent position within the C-terminal SH2 domain.

2 redicted inhibitor binding site to the STAT3 SH2 domain.

3 our LYN mutations, two of which affected the SH2 domain.

4 th over 10-fold higher affinity than the Abl SH2 domain.

5 in the PERK juxtamembrane domain through its SH2 domain.

6 on to existing crystal structures of the Abl SH2 domain.

7 BP-1-102 are predicted to bind to the STAT3 SH2 domain.

8 erved Tyr(P)-binding arginine residue in the SH2 domain.

9 ncreased rigidity of the inhibitor-complexed SH2 domain.

10 their function is highly dependent on their SH2 domain.

11 on of Dock in male germ cells depends on its SH2 domain.

12 e clinical relevance of targeting a specific SH2 domain.

13 anner on Y1311 and Y1320, which bind the Src SH2 domain.

14 otent, small-molecule inhibitor of the STAT3 SH2 domain.

15 s and FLT3-ITD, which is mediated by the SRC SH2 domain.

16 extensive structural rearrangement of the N-SH2 domain.

17 the binding specificity of the overexpressed SH2 domain.

18 ide inhibitor G7-B1 in complex with the Grb7-SH2 domain.

19 ligand binding sites in distal c-Src SH3 and SH2 domains.

20 s and the phosphoSH3C binds de novo to other SH2 domains.

21 actions involving their noncatalytic SH3 and SH2 domains.

22 c the flexibility found in homologous kinase SH2 domains.

23 ent of doubly phosphorylated peptides by the SH2 domains.

24 type FLT3 (FLT3-WT) and FLT3-ITD through the SH2 domains.

25 FR, consistent with the known promiscuity of SH2 domains.

26 hen activated by sequential binding with the SH2 domains.

27 n the SFK SH2 family against the rest of the SH2 domains.

28 nce that SHP2 binding on p85 occurred on the SH2 domains.

29 of binding of a phosphotyrosine in classical SH2 domains.

30 he catalytic domain with the Src Homology 2 (SH2) domain.

31 ding domain and a C-terminal Src homology 2 (SH2) domain.

32 H2) region, and a C-terminal Src-homology-2 (SH2) domain.

33 oteins where tyrosine phosphorylation of the SH2 domain acted as an intramolecular switch for the int

34 inpoint a direct interaction between the LNK SH2 domain and a phosphorylated tyrosine residue in KIAA

35 tin-1 or the adaptor FcRgamma, through its N-SH2 domain and a previously unrecognized carboxy-termina

36 s with the phospho-Y-705-binding site in the SH2 domain and displaces fluorescein-labeled GpYLPQTV ph

37 SOCS2-EphA2 binding requires the SOCS2 SH2 domain and EphA2 activation loop autophosphorylation

38 an intact phosphotyrosine-binding competent SH2 domain and on tyrosine phosphorylation within NS5A.

39 tutively by an interaction between the STATc SH2 domain and phosphotyrosine residues on Pyk2 that are

40 tudies on binding interactions involving the SH2 domain and phosphotyrosine(pTyr)-based inhibitors.

41 the ITK recognition element on the PLCgamma1 SH2 domain and release of the target tyrosine, Y783.

42 ises from interactions between N-cap and the SH2 domain and SH3-SH2 connector, which involve a phosph

43 on and impairs the association between the N-SH2 domain and the catalytic protein tyrosine phosphatas

44 ents and point mutations identified the Nck1 SH2 domain and the first SH3 domain as critical for flow

45 p110alpha complexed with the p85alpha inter-SH2 domain and the inhibitor PIK-108.

46 motif is phosphorylated, with the N-terminal SH2 domain and the ITIM being most important for the int

47 Dimerization of STAT3 via its SH2 domain and the subsequent translocation of the dimer

48 wing protein-protein interaction through the SH2 domain and the Tyr-415 residue of PLD2.

49 nt of the tyrosine kinase Syk via its tandem SH2 domains and initiation of a downstream signaling cas

50 hic effects of mutant Shp2 depend on the two SH2 domains and on an intact catalytic center.

51 with the respective dwell time for different SH2 domains and the dwell time is positively correlated

52 cupy the phosphopeptide-binding sites of the SH2 domains and thus can serve as competitors of SH2-pho

53 binds activated RANK via its Src homology 2 (SH2) domain and alphavbeta3 via its SH3 domain, suggesti

54 ted two tyrosine residues in Src homology 2 (SH2) domain and one tyrosine residue each in calponin ho

55 oth with the DNA binding domain and with the SH2 domain, and (ii) these putative contacts provide pot

56 1 linker enhances binding of the Spt6 tandem SH2 domain, and here we show that Bur1/Cdk9 is the kinas

57 SOCS3 protein binds to Brk primarily via its SH2 domain, and its main inhibitory effect is mediated b

58 privileged structures for antagonizing STAT SH2 domains, and demonstrates that apoptosis can be indu

59 on Src homology 3 (SH3) and Src homology 2 (SH2) domains, and correlated with movement between a per

60 19 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, provid

61 SH2 domains are integral to many animal signaling pathwa

62 Src homology 2 (SH2) domains are 100 amino acid modular units, which rec

63 Src homology 2 (SH2) domains are composed of weakly conserved sequences

64 nd PH domains, along with the BPS region and SH2 domain, are necessary for downregulation of insulin

65 This SH2 domain-based photoprobe was targeted to cellular str

66 H2 domains reveals that approximately 90% of SH2 domains bind plasma membrane lipids and many have hi

67 Our results suggest that signaling via SH2 domain binding is buffered over a relatively wide ra

68 d an in vitro screen of a focused library of SH2 domain binding salicylic acid-containing inhibitors

69 in recruitment correlated with clustering of SH2 domain binding sites on the membrane, consistent wit

70 es are important determinants of Arg and Abl SH2 domain binding specificity.

71 Detailed analysis of c-Src SH2 domain binding to a panel of phosphorylation-deficie

72 which the tyrosine residues responsible for SH2 domain binding were substituted with phenylalanine (

73 ease in the number of unbound phosphorylated SH2 domain-binding sites.

74 ce, which acts as an unusual Src homology 2 (SH2) domain-binding protein activation site of STAT3.

75 We demonstrate that the Vav2 SH2 domain binds selectively to phosphotyrosine-containi

76 ent manner, demonstrating that targeting the SH2 domain blocks both phosphorylation and transcription

77 B4 bicyclic peptide in complex with the Grb7-SH2 domain, both before and after ring closing metathesi

78 This event requires signals from the Abl SH2 domain but not the carboxyl terminus.

79 18NATE) inhibits Grb7 via targeting the Grb7-SH2 domain, but requires the presence of phosphate ions

80 ot retrieved by normal homology searches for SH2 domains, but can be found in many tyrosine kinase-re

81 nonmetazoan with functionally characterized SH2 domains, but the cognate tyrosine kinases are unknow

82 TAT1 that connect the DNA-binding domain and SH2 domain can prevent transcriptional activation.

83 Our results show that SFK SH2 domains can be targeted with unprecedented potency a

84 which propose alternative mutation-mediated SH2 domain conformations.

85 1 (SPRY1) as validating targets, and SPRY2, SH2 domain containing 2A (SH2D2A), and signal transducin

86 we found that the phosphoSH3C binds several SH2 domain containing proteins, including specific non-r

87 A SH2-domain containing inositol-5-phosphatase (SHIP) is a

88 e site may be partially conserved with other SH2-domain containing kinases and therefore offer additi

89 , we found that the scaffold adaptor protein SH2 domain-containing adaptor protein B (Shb) is essenti

90 study, a biochemical approach identified the SH2 domain-containing adaptor protein GADS as the domina

91 EPO-R Tyr(P)-343 and Tyr(P)-401 bind to the SH2 domain-containing adaptor protein SH2B1beta.

92 scaffold proteins followed by recruitment of SH2 domain-containing adaptor proteins constitutes a cen

93 domain-containing phosphatase-1 (SHP-1) and SH2 domain-containing inositol 5 phosphatase were hyperp

94 phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5' phosphatase.

95 ion in Fas(lpr) B cells restored the reduced SH2 domain-containing inositol 5'-phosphatase 1 to norma

96 suppression requires the presence of SHIP1 (SH2 domain-containing inositol 5'-phosphatase 1) and inv

97 Thus, by controlling the levels of SH2 domain-containing inositol 5'-phosphatase 1, miR-155

98 Concomitantly, SH2 domain-containing inositol 5-phosphatase 1 (SHIP1) w

99 nduced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/p

100 vation, and is restored by the activation of SH2 domain-containing inositol 5-phosphatase that inhibi

101 on in NK cells lacking EAT-2 was mediated by SH2 domain-containing inositol phosphatase 1 (SHIP-1), w

102 In this study, we demonstrate that SLP-76 (SH2 domain-containing leukocyte phosphoprotein of 76 kD)

103 We found that the adaptor molecule SH2 domain-containing leukocyte protein of 76 kD (SLP-76

104 Loss of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76

105 SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa) is an

106 The functional effect on RA FLS of SH2 domain-containing phosphatase 2 (SHP-2), a PTP that

107 nd TEM are due to differential regulation by SH2 domain-containing phosphatase-1 (Shp-1) and C-termin

108 Accordingly, both SH2 domain-containing phosphatase-1 (SHP-1) and SH2 doma

109 Cytokine-inducible SH2 domain-containing protein (CISH), a member of the su

110 also confers antiestrogen resistance is the SH2 domain-containing protein BCAR3.

111 signaling by regulating receptor kinase and SH2 domain-containing protein tyrosine phosphatase 2 (Sh

112 The SH2 domain-containing protein-tyrosine phosphatases Shp1

113 H2 domains, SYK and ZAP-70, as well as other SH2 domain-containing proteins such as CSK and PI3K, fro

114 A number of other previously unreported SH2 domain-containing proteins, including Syk and PLCgam

115 ides to investigate the inhibitory effect on SH2 domain-containing proteins.

116 ic moiety into inhibitors designed for other SH2 domain-containing proteins.

117 tant for cellular function and regulation of SH2 domain-containing proteins.

118 utations in the protein tyrosine phosphatase SH2 domain-containing PTP (SHP2), have been shown to dev

119 eptor type 11 (PTPN11) gene that encodes the SH2 domain-containing PTP-2 (SHP2).

120 currently unknown but thought to involve the SH2 domain-containing tyrosine phosphatase SHP-1.

121 s phosphorylated but did not bind the tandem SH2 domain-containing tyrosine phosphatase SHP-2, indica

122 potential role of the ubiquitously expressed SH2 domain-containing tyrosine phosphatase-2 (SHP2) as a

123 ver the recruitment and activation of tandem SH2 domain-containing tyrosine phosphatases that dampen

124 s suggesting that additional Src homology 2 (SH2) domain-containing effectors may bind to EPO-R Tyr-3

125 The adapter protein Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-

126 d protein kinase 70 (Zap70), Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP7

127 Here, we report that Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1) is a major

128 in complex that includes the Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2).

129 proach, we found nonreceptor Src homology 2 (sh2) domain-containing phosphatase Shp2 to be associated

130 PTPN11 encodes SHP2, an Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase that

131 pecific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-

132 subset of approximately 100 Src homology 2 (SH2) domain-containing proteins to the cell membrane.

133 s) recruit and phosphorylate Src Homology 2 (SH2) domain-containing substrates has remained elusive.

134 o sialic acid-containing ligands and recruit SH2-domain-containing tyrosine phosphatases to their cyt

135 stablishes an unusual mechanism by which p85 SH2 domains contribute to RTK signaling specificities.

136 sis and functional analysis to find that the SH2 domain conveys both local and global effects on the

137 ated by random mutagenesis of the C-terminal SH2 domain (cSH2) of PLCgamma1 and isolated a mutant for

138 tyrosine autophosphorylation of Jak3 at the SH2 domain decreased these intramolecular interactions a

139 ments reveal that EPO-R binds to SH2B1 in an SH2 domain-dependent manner and that the sequence that c

140 f cyt-PTPe most prominently, whereas the Src SH2 domain did not bind at all, suggesting that GRB2 may

141 activates a non-receptor tyrosine kinase by SH2 domain displacement.

142 pressed in cells, monobodies targeting the N-SH2 domain disrupted the interaction of SHP2 with its up

143 Mutation of the Vav2 SH2 domain disrupts its recruitment to invadopodia, and

144 Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 aboli

145 utinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizin

146 Mutation R192W in the C-SH2 domain exhibited reduced binding to phosphorylated z

147 ighly unstructured and dynamic nature of the SH2 domain, experimental confirmation of this prediction

148 Grb2 consists of an SH2 domain flanked by N- and C-terminal SH3 domains (nSH

149 We crystallized the Arg SH2 domain for structural comparison to existing crystal

150 ctivates Src, we screened 73 Src homology 2 (SH2) domains for binding to Tyr(P)-638 of cyt-PTPe.

151 Compared to controls expressing a mutant SH2 domain form of EAT-2, Ad5 immune mice vaccinated wit

152 A biosensor based on the tandem SH2 domains from phospholipase C-gamma1 (PLCgamma1), tSH

153 ) it contains the most conserved sequence of SH2 domains, GSFLVR; (ii) it binds the tyrosine phosphor

154 in's function through disrupting that of its SH2 domain has emerged as a promising approach towards t

155 The Src homology 2 (SH2) domain has a highly conserved architecture that rec

156 Although many STAT3 inhibitors targeting the SH2 domain have been reported, few have moved into clini

157 Since 1986, SH2 domains have been identified in over 110 human prote

158 The Hck SH2 domains impinge on the N-terminal region of Nef to s

159 ed Src bound K6-containing filaments via its SH2 domain in a novel phosphorylation-independent manner

160 wed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and the

161 l SH2 domain to a higher affinity "Arg-like" SH2 domain in binding to a phospho-cortactin peptide.

162 Ectopic expression of the SH2 domain in cells was sufficient to counter the STAT3-

163 707Q) in the highly conserved autoinhibitory SH2 domain in three of 10 cases.

164 etic agents that disrupt the function of the SH2 domains in different proteins as well as the clinica

165 or C-SH2 revealed distinct roles of the two SH2 domains in downstream signaling, such as the phospho

166 In line with the critical roles of SFK SH2 domains in kinase autoinhibition and T-cell receptor

167 Likewise, mutations of the SH3.1 and SH2 domains in Nck1 resulted in the loss of Nck1 binding

168 etween phosphorylated CaM (pCaM) and the two SH2 domains in the p85 subunit, confirm experimental obs

169 t interaction with the Hck SH3 or tandem SH3-SH2 domains induces protection of the Nef alphaB-helix f

170 SH3 and SH2 domains inhibit Abl by assembling onto the catalytic

171 unds showed high-affinity binding to Stat3's SH2 domain, inhibited intracellular Stat3 phosphorylatio

172 The SH2 domain inhibitors could potentially serve as drug ca

173 ent of pharmacological STAT3 Src homology 2 (SH2) domain interaction inhibitors holds great promise f

174 ndicate a hitherto unrecognized diversity in SH2 domain interactions with phosphotyrosine and classif

175 ntegrin-rich complex, which depended on GRB7-SH2 domain interactions.

176 on factors that dimerize via phosphotyrosine-SH2 domain interactions.

177 Although targeting the SH2 domain is a challenging task in molecular recognitio

178 Although the SH2 domain is a less common binding interface in Shc pro

179 and pY580, for cis-interaction with the same SH2 domain is governed by an antagonistic combination of

180 s using SPR confirmed that affinity for Grb7-SH2 domain is improved up to 9-fold over peptide 1 under

181 A hallmark of SH2 domains is the arginine residue in the conserved FLV

182 The Src-homology 2 (SH2) domain is a protein interaction domain that directs

183 LCK may also interact with TSAD through its SH2 domain, ITK interacts with TSAD only through its SH3

184 imately 2-fold enhanced affinity to the Grb7-SH2 domain (KD = 0.83 muM) compared to G7-B1 and shows l

185 affinity binding to Grb2-, Grb10- and Grb14-SH2 domains (KD > 100 muM).

186 aining an "Abl-like" low affinity mutant Arg SH2 domain (L207R/T233S) and find that this mutant, alth

187 Phospho-Y14 interacts with the Src SH2 domain, leading to the phosphorylation of two additi

188 Other SH2 domain LYN mutants, E159K and K209N, also exhibited

189 s of allosteric perturbations outside of the SH2 domain, manifesting mainly as increased deuterium up

190 phosphorylation status, suggesting that the SH2 domains mediate interactions with activated receptor

191 ively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction

192 2-mCAT-1 binding does not depend on the GRB2-SH2 domain-mediated recognition of tyrosine phosphorylat

193 paring SH2 binding site phosphorylation with SH2 domain membrane recruitment in living cells, we foun

194 In an unbiased screen using a SH2 domain microarray we identified the SH2 domain of gr

195 rupts its recruitment to invadopodia, and an SH2-domain mutant form of Vav2 cannot support efficient

196 There was no evidence of STAT3 SH2 domain mutation or activation.

197 ) peptide binding to the p85alpha N-terminal SH2 domain (nSH2) induces lipid binding.

198 by facilitating NS5A's interaction with the SH2 domain of c-Src.

199 The SH2 domain of Csk is an essential component for the down

200 A unique feature of the SH2 domain of Csk is the tight turn in place of the cano

201 experiments, we demonstrated the role of the SH2 domain of Ctr9 in nuclear localization.

202 We also studied the binding of the isolated SH2 domain of Grb2 (growth factor receptor-bound protein

203 The SH2 domain of GRB2 bound Tyr(P)-638 of cyt-PTPe most pro

204 a tyrosylphosphate-containing ligand to the SH2 domain of Grb2, results in dimer dissociation.

205 and was responsible for Nox4 binding to the SH2 domain of Grb2.

206 ng a SH2 domain microarray we identified the SH2 domain of growth factor receptor-bound protein 14 (G

207 However, the SH2 domain of Jak3 prevented P-villin-wt from binding to

208 y-conserved three-dimensional structure, the SH2 domain of M. brevicollis crka1 can bind to the mamma

209 e X-ray crystal structures of the C-terminal SH2 domain of p120RasGAP (RASA1) in its apo and peptide-

210 phosphotyrosine and classify the C-terminal SH2 domain of p120RasGAP as "FLVR-unique."

211 with significant affinity to the C-terminal SH2 domain of PLCgamma1 (SH2C).

212 We determined that the tandem SH2 domain of S. cerevisiae Spt6 binds the linker region

213 ix cap to helix alphaB within the N-terminal SH2 domain of Shp2, whereas Ser-189 occupies an equivale

214 LAT family-independent pathway involved the SH2 domain of SLP-76 and adhesion and degranulation-prom

215 as two N-terminal-located tyrosines and the SH2 domain of SLP-76 are required for downstream signali

216 s known about the function of the C-terminal SH2 domain of SLP-76.

217 al motif that includes tyrosine (Y)80 in the SH2 domain of SOCS1.

218 mental structures of inhibitors bound to the SH2 domain of STAT3 are, however, unavailable.

219 of 12 peptidomimetic inhibitors bound to the SH2 domain of STAT3.

220 loping phosphopeptide mimetics targeting the SH2 domain of STAT6 to block recruitment to phosphotyros

221 The site(s) that are generated bind the SH2 domain of STATc, and then STATc becomes the target o

222 of phosphotyrosine binding of the N-terminal SH2 domain of Syk on platelet activation by GPVI, CLEC-2

223 dentified a D189Y mutation in the inhibitory SH2 domain of the SRC family kinase (SFK) LYN.

224 ll as the intact phosphotyrosine-interacting SH2 domain of VAV3, are necessary for this interaction.

225 ramolecular interaction between the FERM and SH2 domains of nonphosphorylated Jak3 prevented Jak3 fro

226 tment with a molecule composed of the tandem SH2 domains of PLCgamma2.

227 nteractions to be direct and that the tandem SH2 domains of SHP-2 demonstrated a binding affinity for

228 ts delineate a hierarchy of function for the SH2 domains of SHP2 and validate monobodies as potent an

229 termed monobodies, for the N- and C-terminal SH2 domains of SHP2.

230 in complex with either the SH3 or tandem SH3-SH2 domains of Src-family kinases reveal distinct dimer

231 pon phosphorylation these tyrosines bind the SH2 domains of the Ras inhibitor p120 RasGAP.

232 one and in complexes with the SH3 or the SH3-SH2 domains of the Src-family kinase Hck.

233 raction between NS5A and the Src homology 2 (SH2) domain of c-Src; however, the precise binding mode

234 63 ubiquitination within the Src homology 2 (SH2) domain of STAT3, which is an essential step for STA

235 omone-based inhibitor of the Src homology 2 (SH2) domain of the transcription factor STAT5 confer inh

236 that overexpress the tandem Src homology 2 (SH2) domains of PLCgamma2 (SH2(N+C)) failed to form matu

237 odels, we develop fusions of Src homology 2 (SH2) domain or a phosphorylatable SH2-binding peptide, r

238 ling and biochemical analyses suggested that SH2 domain overexpression does not result in a major dec

239 We analyzed the effects of SH2 domain overexpression on protein tyrosine phosphoryl

240 ally, we show for the first time how the SH3-SH2 domains perturb the dynamics of the kinase domain in

241 cells, activates the Src homology region 2 (SH2) domain -phosphatases SHP-1 and SHP-2 in macrophages

242 ramework that draws on biophysical data from SH2 domain-phosphoprotein interactions to predict the fu

243 trategy is to design inhibitors blocking its SH2 domain phosphotyrosine binding site that is responsi

244 While the affinities and specificities of SH2 domain-phosphotyrosine interactions have been well c

245 or understanding the evolutionary origins of SH2 domain-phosphotyrosine signaling.

246 high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively

247 Using high-throughput SH2 domain profiling, artificial neural network and posi

248 roscopic studies demonstrated that the Grb14 SH2 domain promoted the rapid recruitment of this adapto

249 ls through SLAM-associated protein (SAP), an SH2 domain protein that can function by the recruitment

250 de range of effector concentrations and that SH2 domain proteins with overlapping binding specificiti

251 rosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domai

252 valuate the interactions of human MERTK with SH2-domain proteins present in the RPE.

253 In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(57

254 TK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both

255 this issue, we designed variants of the Grb2 SH2 domain ("pY-clamps") whose specificity is highly bia

256 ed conformation recapitulating the canonical SH2 domain-pY pose, but capture different conformations

257 Delayed SH2 domain recruitment correlated with clustering of SH2

258 l in which binding of Syk via its N-terminal SH2 domain regulates autophosphorylation.

259 d to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase ac

260 new interactions but that mutations altering SH2 domains result almost exclusively in loss of interac

261 The binding of both inhibitors to the SH2 domain resulted in significant local decreases in dy

262 Conversely, mutation of the ShcD SH2 domain results in enhanced repression of Erk.

263 library in complex with its target, the Abl SH2 domain, revealed that a concave surface of the monob

264 Genome-wide screening of human SH2 domains reveals that approximately 90% of SH2 domain

265 ignaling, monobodies binding the Src and Hck SH2 domains selectively activated respective recombinant

266 well as against STAT3 and STAT1 proteins for SH2 domain selectivity.

267 Identification of the SH2-domain signaling partners of MERTK is an important s

268 nally, we uncover similar properties driving SH2 domain specificity and demonstrate how the identific

269 t the interaction between NS5A and the c-Src SH2 domain strictly depends on an intact phosphotyrosine

270 f glutamic acid for tyrosine between the Syk SH2 domains (Syk-Y130E) led to an increased Syk-Fcepsilo

271 ding two signaling kinases possessing tandem SH2 domains, SYK and ZAP-70, as well as other SH2 domain

272 itro and in cells and whose affinity for its SH2-domain target exhibits a 330-fold shift in binding a

273 ott-Aldrich syndrome protein (N-WASP) and an SH2 domain that binds to multiple phosphotyrosine sites

274 substitution is located in an autoinhibitory SH2 domain that is crucial for PLCgamma2 activation.

275 role for a phosphosite, Y192, within the Lck SH2 domain that profoundly affects the amount of active

276 hat involves deformation of two loops of the SH2 domain that subsequently bury the C-terminal end of

277 tor Vav2 in a comprehensive screen for human SH2 domains that bind selectively to phosphorylated cort

278 nnatural amino acid-modified Src homology 2 (SH2) domain that is expressed within cells and can coval

279 e sufficient to convert the low affinity Abl SH2 domain to a higher affinity "Arg-like" SH2 domain in

280 re efficiently than did Btk and required its SH2 domain to perform these functions.

281 -14 by Src and subsequent binding of the Src SH2 domain to phospho-Cav-1, leading to accumulation of

282 ich involves reciprocal binding of the STAT3-SH2 domain to phosphorylated tyrosine-705 (Y-705), is re

283 tivated by phosphorylation or binding of its SH2 domains to a dual-phosphorylated immune-receptor tyr

284 ally attributed to cis binding of its tandem SH2 domains to dual phosphotyrosines within FcepsilonRIg

285 n recruitment of Syk via docking of its dual SH2 domains to phosphorylated tyrosines within the Fceps

286 The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical f

287 teracts with phosphorylated MET via the TNS4 SH2-domain to positively regulate cell survival, prolife

288 r that binds with high affinity to the STAT3 SH2 domain triggers a complex cascade of events initiate

289 ipitation and pulldown assays, ShcA, via its SH2 domain, was associated with several phosphorylated t

290 e high structural similarity between the two SH2 domains, we observe that nSH2 prefers an extended Ca

291 ssion of p120RasGAP Src homology 2 (SH2)-SH3-SH2 domains, which interact with the C-terminal tail of

292 ted in exon 21, encoding the Src homology 2 (SH2) domain, which mediates the dimerization and activat

293 nally S-palmitoylated at the SRC homology 2 (SH2) domain, which promotes the dimerization and transcr

294 rk of subtle structural shifts that link the SH2 domain with the activation loop and the active site

295 teins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity.

296 We constructed Abl SH2 domains with R161L and S187T mutations alone and in

297 ptides, such as those of the Src homology 2 (SH2) domain with phosphotyrosine-containing peptide moti

298 between the C-terminal phosphotyrosines and SH2 domain within the protein tyrosine phosphatase Shp2

299 We conclude that expression of SH2 domains within cellular compartments that are capabl

300 rm to the canonical recognition motif for an SH2 domain yet binds with significant affinity to the C-