ライフサイエンスコーパス: LAT1

1 LAT1 (SLC7A5) is a transporter for both the uptake of la

2 LAT1 (SLC7A5) transports large neutral amino acids and p

3 LAT1 and SNAT2 protein content increased during the post

4 LAT1 deletion in keratinocytes does not dampen the infla

5 LAT1 deletion or inhibition blocks expansion of IL-17-se

6 LAT1 expression in bladder cancer cells was higher than

7 LAT1 expression is increased in keratinocytes and skin-i

8 LAT1 expression was evaluated via immunohistochemistry a

9 LAT1 features a canonical Leu T-fold and exhibits an unu

10 LAT1 floxed mice were crossed to Cre-expressing mouse st

11 LAT1 forms a disulfide-linked heterodimer with CD98 heav

12 LAT1 is overexpressed in several types of tumors, and it

13 LAT1 uptake was tolerant of fluorinated amino acid stere

14 LAT1 was also identified on human cornea.

15 LAT1 was identified by RT-PCR in rabbit corneal, SIRC, a

16 LAT1-dependent calcium signals required for mast cell de

17 LAT1/LAT2/CD98 was strongly expressed in neurons and end

18 The L-type amino acid transporter 1 (LAT1 or SLC7A5) transports large neutral amino acids acr

19 hibition of l-type amino acid transporter 1 (LAT1) and GCN2 significantly inhibited growth of ASCT2ko

20 The l-type amino acid transporter 1 (LAT1) is a transmembrane protein carrying bulky and neut

21 L-type amino acid transporter 1 (LAT1) plays a role in transporting essential amino acids

22 L-type amino acid transporter 1 (LAT1), also referred to as SLC7A5, is believed to regula

23 L-type amino acid transporter 1 (LAT1), which is encoded by solute carrier transporter 7a

24 ated by the l-type amino acid transporter-1 (LAT1) but is less sensitive to natural amino acid compet

25 l-amino acid transporter-1 (LAT1) is a highly conserved gene identified as a light c

26 for large neutral amino acid transporter-1 (LAT1) was performed on total RNA from rabbit cornea, SIR

27 y described for the chimeric virus HSV-2 333/LAT1 and indicate that the HSV-1 latency phenotype can b

28 Comparison of SLP-76(-/-) LAT1(-/-) and SLP-76(-/-) mast cells revealed that some

29 ential AA and impaired mTORC1 signaling in a LAT1-dependent manner.

30 ase Fgr and shifted signals from the adapter LAT1 to the related adapter LAT2.

31 We hypothesize that the altered LAT1 expression observed in hepatocarcinogenesis gives c

32 encoding MCT8, MCT10, OATP3A1 variant 1 and LAT1 were similar.

33 We propose that while SLP-76 and LAT1 depend on each other for many of their functions, L

34 ucleated by the adaptor molecules SLP-76 and LAT1 is required for activation through this receptor.

35 AT1(-/-) mast cells and that SLP-76(-/-) and LAT1(-/-) mast cells harbored distinct functional and bi

36 on of the Gln transporters SNAT1, ASCT2, and LAT1 by CD138(+) cells across the progression of monoclo

37 ystem A amino acid transporter isoforms) and LAT1 and LAT2, but not CD98, (System L amino acid transp

38 A), SN1 and SN2 (isoforms of system N), and LAT1 and LAT2 (isoforms of system L) were investigated i

39 3 and the amino acid transporters SLC1A5 and LAT1, directing them to lysosomes and permitting efficie

40 f neuronal, endothelial, and less astroglial LAT1/LAT2/CD98 amino acid transporter expression.

41 Northern blotting with the bovine BBB LAT1 cDNA showed that the LAT1 mRNA is 100-fold higher i

42 into frog oocytes coinjected with bovine BBB LAT1 mRNA and the mRNA for 4F2hc, which encodes the heav

43 The bovine BBB LAT1 mRNA produced a 10-fold enhancement in tryptophan t

44 We assessed the relationships between LAT1 expression and patient outcomes and clinicopatholog

45 Both LAT1 and LAT2, when co-expressed with 4F2 heavy chain, w

46 ules at the interface and C-terminus of both LAT1 subunits.

47 reast cancer-specific survival stratified by LAT1 expression was assessed.

48 l-L-leucine as a prodrug of leucine bypasses LAT1, the rate-limiting step in activation of leucine-me

49 Slc7a5, which encode the heterodimeric CD98 (LAT1/4F2hc) amino acid transporter and regulate the intr

50 nhibition of the amino acid transporter CD98/LAT1 abrogated the leucine-driven mTORC1 activation and

51 expression of the nutrient transporter CD98/LAT1 for amino acids independently of the mTORC1 pathway

52 nvert the substrate profiles of LAT2/CD98hc, LAT1/CD98hc, and Asc1/CD98hc.

53 nd compensates for impaired uptake of CD98hc/LAT1 and CD98hc/y(+)LAT2.

54 Collectively, LAT1 significantly contributed to bladder cancer progres

55 In conclusion, LAT1 is modulated by cholesterol impacting on its stabil

56 This mutant, LAT3.3A (previously designated LAT1.5a), thus showed that the expression of just the fi

57 Mammalian cells were shown to express LAT1 and LAT2.

58 tion of leucine that has a high affinity for LAT1 should prevent the entry of kynurenine into the bra

59 embrane, LAT2 only partially compensated for LAT1-mediated cell signaling due to its decreased abilit

60 indirectly, suggesting a potential role for LAT1 in bone homeostasis.

61 o provide evidence of super-dimer formation (LAT1-4F2hc)(2).

62 sion of key transporter proteins (glutamine: LAT1, LAT2, SNAT5, glutamate: EAAT1) versus AGA [IBR 20t

63 High LAT1 was related to the high Grade, pathological T stage

64 In conclusion, high LAT1 expression could be used to identify a subgroup of

65 Moreover, high LAT1 expression was an independent poor prognostic facto

66 ER-positive and HER2-negative patients, high LAT1 was an independent indicator of poor outcomes (haza

67 In the current study, high LAT1 expression was significantly correlated with estrog

68 Multivariate analysis revealed that high LAT1 expression was found as an independent prognostic f

69 Patients with high LAT1 and IGFBP-5 expression had significantly shorter ov

70 that in C. elegans an ortholog of the human LAT1 transporter, AAT-1, imports Kyn into sites of KynA

71 we report the cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.3- angstrom resolution.

72 Here, we identified LAT1 in osteoclasts as important for bone homeostasis.

73 These data definitively identify LAT1 and LAT2 as members of system L that mediate transm

74 ocalization and phosphorylation of SLP-76 in LAT1(-/-) mast cells.

75 ransport activity correlates with changes in LAT1.

76 was associated with a selective increase in LAT1 mRNA and protein.

77 phosphorylation of SLP-76 were preserved in LAT1(-/-) mast cells and that SLP-76(-/-) and LAT1(-/-)

78 assess the functional relevance of increased LAT1 expression and the requirement for 4F2 heavy chain,

79 2/SLP-76 interactions and SLP-76-independent LAT1 functions also mediate a positive signaling pathway

80 The capacity of vascular mitogens to induce LAT1 expression may represent a basic mechanism by which

81 e stimulated L-leucine transport by inducing LAT1 expression.

82 te system L amino acid transport by inducing LAT1 gene expression and that system L amino acid transp

83 nd IL-23 and tested the effect of inhibiting LAT1 (JPH203) and mammalian target of rapamycin (mTOR [r

84 However, known LAT1 inhibitors lack selectivity over other transporters

85 The system L LAT1/4F2hc amino acid transporter was examined through u

86 ific System A (SNAT2, SLC38A2) and System L (LAT1, SLC7A5) transporter isoforms without affecting glo

87 -treated tumors showed only weak or marginal LAT1 staining, whereas CD98 staining remained unchanged.

88 accompanied by reduced expressions of MCT8, LAT1, CD98 and OATP4A1.

89 rs mediate uptake, we expressed two members, LAT1 and LAT2, in Xenopus oocytes.

90 embers of the 4F2 light chain family, namely LAT1 (4F2-lc1), y(+)LAT1 (4F2-lc2), y(+)LAT2 (4F2-lc3),

91 regulation of palmitoylation on neighbouring LAT1-C187.

92 e further validate the dynamic assemblies of LAT1-4F2hc on plasma membrane and in the lysosome.

93 Immunohistochemical assessment of LAT1/LAT2/CD98 amino acid transporters was performed in

94 Specific deletion of LAT1 in gammadelta and CD4 T cells controls the inflamma

95 nterest in view of the ongoing evaluation of LAT1 substrates and inhibitors for cancer therapy.

96 lation leading to constitutive expression of LAT1 can contribute to oncogenesis.

97 ous studies we found increased expression of LAT1 in primary human cancers.

98 ) 18.5, in line with increased expression of LAT1, a glutamine transporter protein.

99 ed with ATF4 and regulated the expression of LAT1, an essential AA transporter.

100 ) mast cells revealed that some functions of LAT1 could occur independently of SLP-76.

101 ine transport and was largely independent of LAT1 and leucine, which explains why leucine could block

102 The induction of LAT1 by PDGF was dependent on de novo RNA and protein sy

103 Moreover, inhibition of LAT1 blocks expansion of human gammadelta T cells and IL

104 Deletion or inhibition of LAT1 efficiently controls IL-23- and IL-1beta-induced ph

105 for substrate recognition and inhibition of LAT1, guiding future drug design.

106 activity of JPH203, a specific inhibitor of LAT1, was studied in bladder cancer.

107 Overexpression of LAT1 alone in mouse hepatocytes, but not fibroblasts, wa

108 Overexpression of LAT1 in T24 cells using recombinant adenoviruses led to

109 he expression profile and functional role of LAT1 in bladder cancer.

110 Here we report six structures of LAT1 across three conformations with bound ligands, eluc

111 Amino acid substrates of LAT1 have a beneficial effect on bone health directly an

112 cent advances in structural understanding of LAT1, how it discriminates substrates and inhibitors inc

113 inhibitor (1), which inhibited the uptake of LAT1 substrate, l-leucin as well as cell growth.

114 copathologically investigated the utility of LAT1 expression.

115 oth proteins, whereas T24 cells express only LAT1.

116 e designed and synthesized a novel selective LAT1 inhibitor (1), which inhibited the uptake of LAT1 s

117 human glutamine transporters ASCT2 (SLC1A5), LAT1 (SLC7A5), SNAT1 (SLC38A1), and SNAT2 (SLC38A2), we

118 (SLC38A1), SNAT2 (SLC38A2), SNAT4 (SLC38A4), LAT1 (SLC7A5), and ASCT2 (SLC1A5).

119 anscripts specific for ATA1, ATA2, SN1, SN2, LAT1, and LAT2 were expressed in Muller cells.

120 -independent, facilitative transport system, LAT1, was identified and functionally characterized on r

121 Targeting LAT1 by JPH203 may represent a novel therapeutic option

122 Targeting LAT1-mediated amino acid uptake is a potentially useful

123 g preclinical drugs and antibodies targeting LAT1 or CD98hc.

124 We have demonstrated also that LAT1 response to arginine availability is lost in transf

125 T-cell studies, current dogma dictates that LAT1 is required for plasma membrane recruitment and fun

126 Our findings suggest that LAT1 might be a candidate therapeutic target for breast

127 The LAT1-4F2hc complex (SLC7A5-SLC3A2) facilitates uptake of

128 The LAT1-like molecule LAT2 was responsible for the preserve

129 th C6 rat glioma cells or rat brain, and the LAT1 mRNA was not detected in rat liver, heart, lung, or

130 ter than 95% in all tested cell lines by the LAT1/2 inhibitor 2-amino-2-norboranecarboxylic acid.

131 Deleting the LAT1 gene abolishes life span extension induced by CR.

132 interacts with the conserved regions in the LAT1 transporter that have been shown to bind to cholest

133 identifies SLFN5 as a novel regulator of the LAT1 amino acid transporter and an essential contributor

134 terol reduced the Vmax but not the Km of the LAT1 mediated uptake of a model substrate into cells (L-

135 with other tissues, and the abundance of the LAT1 mRNA at the BBB is manyfold higher than that of tra

136 required for the stable purification of the LAT1 with its chaperon CD98 (4F2hc,SLC3A2) and that this

137 ding with regulation and localisation of the LAT1-4F2hc super-dimer.

138 ith the bovine BBB LAT1 cDNA showed that the LAT1 mRNA is 100-fold higher in isolated bovine brain ca

139 These studies show that the LAT1 transcript is selectively expressed at the BBB comp

140 These findings suggest that the LAT1-mTORC1 axis plays a pivotal role in bone resorption

141 no acid sequence was 89-92% identical to the LAT1 isoform.

142 The level of one of these, LAT1, is increased in many tumors.

143 kinetics of MCT1 (lower affinity compared to LAT1) and the ubiquitous tissue expression of MCT1 make

144 as metabolically stable and selective toward LAT1.

145 induction of the amino acid (AA) transporter LAT1 and enhanced expression of the glucose transporter

146 ses the large neutral amino acid transporter LAT1 (SLC7A5) in cells.

147 e at the level of the amino acid transporter LAT1 for brain uptake.

148 nto the brain by the large amino transporter LAT1 at the level of the blood-brain barrier.

149 ells from the L-type amino acid transporter (LAT1) used by leucine to organic anion transporters (OAT

150 ndent, large neutral amino acid transporter, LAT1, on rabbit corneal epithelium and human cornea.

151 on of the SNAT2 or the System L transporter, LAT1, suppressed mTOR activation by arsenite, supporting

152 l and small neutral amino acid transporters (LAT1, SNAT2) and CD98], and myofibrillar protein synthes

153 rge, neutral L-type amino acid transporters (LAT1-LAT4) are sodium-independent transporters that are

154 an anticancer drug in clinical trials, traps LAT1 in an outward-facing state with a U-shaped conforme

155 or tumor imaging and quantification of tumor LAT1 activity.

156 IL-23 and IL-1beta stimulation upregulates LAT1 expression and induces mTOR activation in IL-17(+)

157 of three (18)F-labeled leucine analogues via LAT1 mediated transport in several cancer cell lines is

158 endocrine and nonendocrine tumor models via LAT1 transport but is not decarboxylated by AADC.

159 BTS boron delivery appears to correlate with LAT1 expression.

160 CD98hc engages with LAT1 through the extracellular, transmembrane and putati

161 CD98hc-associated transporters (i.e. xCT, LAT1, and y(+)LAT2 in wild-type cells) are crucial to co

162 e and plasma membrane levels of CAT1 and y(+)LAT1 amino acid transporters in endothelial cells.

163 ght chain family, namely LAT1 (4F2-lc1), y(+)LAT1 (4F2-lc2), y(+)LAT2 (4F2-lc3), xCT (4F2-lc4), and L

164 A7, which encodes the light subunit of the y+LAT1 transporter.