ライフサイエンスコーパス: SH2 domain

1 the binding specificity of the overexpressed SH2 domain.

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

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

4 in the PERK juxtamembrane domain through its SH2 domain.

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

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

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

8 ncreased rigidity of the inhibitor-complexed SH2 domain.

9 their function is highly dependent on their SH2 domain.

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

11 e clinical relevance of targeting a specific SH2 domain.

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

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

14 extensive structural rearrangement of the N-SH2 domain.

15 es phosphorylation of S652 in the C-terminal SH2 domain.

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

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

18 redicted inhibitor binding site to the STAT3 SH2 domain.

19 actions involving their noncatalytic SH3 and SH2 domains.

20 c the flexibility found in homologous kinase SH2 domains.

21 ent of doubly phosphorylated peptides by the SH2 domains.

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

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

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

25 of binding of a phosphotyrosine in classical SH2 domains.

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

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

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

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

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

31 pleckstrin homology (PH) and Src homology 2 (SH2) domains.

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

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

34 mined for complex formation between the Grb2 SH2 domain and Ac-pTyr-Xaa-Asn derived tripeptides in wh

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

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

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

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

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

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

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

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

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

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

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

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

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

48 striking structural similarity with metazoan SH2 domains and possesses structural features associated

49 only non-metazoan with functionally analyzed SH2 domains and studying them can give insights into the

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

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

52 otein interaction modules, a Src homology 2 (SH2) domain and a Src homology 3 (SH3) domain.

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 he Y169/Y179 residues of PLD2 using its only SH2 domain, and it interacts with the poly-proline regio

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

58 found that tyrosine 204 of the SOCS box, the SH2 domain, and the N-terminal kinase inhibitory region

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

60 phospho-tyrosine binding pockets of the two SH2 domains, and in the crystal structures the phosphate

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

62 19 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, provid

63 SH2 domains are integral to many animal signaling pathwa

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

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

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

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

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

69 Studies show SPI and Stat3 (or Stat3 SH2 domain) bind with similar affinities to known Stat3-

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

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

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

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

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

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

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

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

78 The Vav SH2 domain binds Syk linker B by an unusual recognition

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

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

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

82 18NATE) inhibits Grb7 via targeting the Grb7-SH2 domain, but requires the presence of phosphate ions

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

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

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

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

87 1 (SPRY1) as validating targets, and SPRY2, SH2 domain containing 2A (SH2D2A), and signal transducin

88 ysically and functionally with CldA, another SH2 domain containing protein.

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

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

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

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

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

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

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

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

97 e-based inhibitory motif phosphorylation and SH2 domain-containing inositol 5'-phosphatase 1 activati

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

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

100 IB by Src kinase and resulting activation of SH2 domain-containing inositol 5'-phosphatase 1, and con

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

102 eceptor tyrosine-based inhibitory motif, and SH2 domain-containing inositol 5'-phosphatase 1.

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

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

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

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

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

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

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

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

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

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

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

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

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

116 Protein tyrosine phosphatase 1B (PTP1B) and SH2 domain-containing protein tyrosine phosphatase-2 (SH

117 The SH2 domain-containing protein-tyrosine phosphatases Shp1

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

119 ee tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

142 irst case in which it has been found that an SH2 domain could colocalize a ubiquitin ligase and its s

143 es an inhibitory function for the C-terminal SH2 domain (cSH2) of the p85 regulatory subunit.

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

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

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

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

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

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

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

151 nterface are reflective of those observed in SH2 domain evolution.

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

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

154 the relative binding affinities of the Vav1 SH2 domain for singly and doubly phosphorylated linker B

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

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

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

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

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

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

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

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

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

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

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

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

167 707Q) in the highly conserved autoinhibitory SH2 domain in three of 10 cases.

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

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

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

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

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

173 phopeptide binds specifically to a subset of SH2 domains, including Abl and Arg SH2, and that binding

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

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

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

177 The SH2 domain inhibitors could potentially serve as drug ca

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

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

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

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

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

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

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

185 omain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation

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

187 hotyrosine phosphatases, and Src Homology 2 (SH2) domains-is a relatively new innovation.

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

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

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

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

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

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

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

195 2-mCAT-1 binding does not depend on the GRB2-SH2 domain-mediated recognition of tyrosine phosphorylat

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

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

198 6 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells.

199 LP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 do

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

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

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

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

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

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

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

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

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

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

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

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

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

213 t a Y4F BCAP mutant defective in binding the SH2 domain of p85 PI3K, reversed the proapoptotic phenot

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

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

216 and that this interaction occurs between the SH2 domain of SHP-1 and the C terminus of GIV.

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

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

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

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

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

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

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

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

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

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

227 A mutation in the SH2 domain of TNS4 prevents the transition from extensio

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

229 o serine residues at analogous sites on both SH2 domains of p85alpha (S361 and S652).

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

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

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

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

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

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

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

237 63 ubiquitination within the Src homology 2 (SH2) domain of STAT3, which is an essential step for STA

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

239 specific clones (recognizing Src homology 2 (SH2) domains of LYN, VAV1, NCK1, ZAP70, PTPN11, CRK, LCK

240 in the iSH2 (inter-SH2) and nSH2 (N-terminal SH2) domains of p85alpha, the regulatory subunit of phos

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

259 Delayed SH2 domain recruitment correlated with clustering of SH2

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

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

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

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

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

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

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

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

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

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

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

271 f the Spt6 C-terminal region reveal a tandem SH2 domain structure composed of two closely associated

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

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

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

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

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

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

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

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

280 ory subunit of PI3K contains Src homology-2 (SH2) domains that mediate binding to tyrosine-phosphoryl

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

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

283 -14 by Src and subsequent binding of the Src SH2 domain to phospho-Cav-1, leading to accumulation of

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

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

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

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

296 simulation of sequences threaded through the SH2 domains, with selective pressures to fold and bind s

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

298 Specifically, we identify the C-terminal SH2 domain within the X/Y linker as the critical determi

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-