ABCG1 p.Ser389Asp
Predicted by SNAP2: | A: N (82%), C: N (57%), D: N (82%), E: N (93%), F: D (53%), G: N (82%), H: N (82%), I: N (72%), K: N (93%), L: N (78%), M: N (82%), N: N (97%), P: N (78%), Q: N (93%), R: N (87%), T: N (93%), V: N (82%), W: D (59%), Y: D (53%), |
Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: D, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, T: N, V: N, W: D, Y: D, |
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[hide] Protein kinase A modulates the activity of a major... J Lipid Res. 2012 Oct;53(10):2133-40. doi: 10.1194/jlr.M028795. Epub 2012 Aug 7. Gelissen IC, Sharpe LJ, Sandoval C, Rao G, Kockx M, Kritharides L, Jessup W, Brown AJ
Protein kinase A modulates the activity of a major human isoform of ABCG1.
J Lipid Res. 2012 Oct;53(10):2133-40. doi: 10.1194/jlr.M028795. Epub 2012 Aug 7., [PMID:22872754]
Abstract [show]
ABCG1 is an ABC half-transporter that exports cholesterol from cells to HDL. This study set out to investigate differences in posttranslational processing of two human ABCG1 protein isoforms, termed ABCG1(+12) and ABCG1(-12), that differ by the presence or absence of a 12 amino acid peptide. ABCG1(+12) is expressed in human cells and tissues, but not in mice. We identified two protein kinase A (PKA) consensus sites in ABCG1(+12), absent from ABCG1(-12). Inhibition of PKA with either of two structurally unrelated inhibitors resulted in a dose-dependent increase in cholesterol export from cells expressing ABCG1(+12), whereas ABCG1(-12)-expressing cells were unaffected. This was associated with stabilization of the ABCG1(+12) protein, and ABCG1(+12)-S389 was necessary to mediate these effects. Mutation of this serine to aspartic acid, simulating a constitutively phosphorylated state, resulted in accelerated degradation of ABCG1(+12) and reduced cholesterol export. Engineering an equivalent PKA site into ABCG1(-12) rendered this isoform responsive to PKA inhibition, confirming the relevance of this sequence. Together, these results demonstrate an additional level of complexity to the posttranslational control of this human ABCG1 isoform that is absent from ABCG1(-12) and the murine ABCG1 homolog.
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No. Sentence Comment
145 Figure 5A shows that basal cholesterol export from ABCG1(+12)-S389D- expressing cells was reduced compared with that of the wild-type ABCG1(+12), whereas incubation with H89 did not affect the cholesterol export capacity to HDL.
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ABCG1 p.Ser389Asp 22872754:145:62
status: NEW178 Fig. 5. Effect of H89 on ABCG1(+12)-S389D cholesterol export and protein levels.
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ABCG1 p.Ser389Asp 22872754:178:36
status: NEW179 A: Cholesterol export was measured as described inthelegendtoFig.2andMaterialsandMethodsfromABCG1(+12)- S389D-overexpressing cells and compared with the parental ABCG1(+12) cell line, with and without the addition of H89 (10 òe;M).
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ABCG1 p.Ser389Asp 22872754:179:104
status: NEW180 B: ABCG1(+12)-S389D-overexpressing cells were incubated with or without H89 in the presence of cycloheximide (10 òe;g/ml), as described in the legend to Fig. 4.
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ABCG1 p.Ser389Asp 22872754:180:14
status: NEW