ABCG1 p.Ser389Ala
| 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
137 Comparison of ABCG1 mRNA expression among the lines showed that expression was similar among the lines, with the exception of the S389A mutant ,which had approximately half the mRNA expression compared with the other cell lines (see supplementary Fig. IIIA).
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ABCG1 p.Ser389Ala 22872754:137:130
status: NEW141 However, HDL-mediated cholesterol efflux from the S389A mutant was on average slightly higher than the parental line, despite having lower mRNA expression, whereas cholesterol export from this mutant was completely unaffected by H89 treatment (Fig. 4).
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ABCG1 p.Ser389Ala 22872754:141:50
status: NEW177 H89 significantly increased cholesterol export from cells expressing ABCG1(+12), S388A, and S390A (P < 0.05), but not ABCG1(afa;12) or S389A.
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ABCG1 p.Ser389Ala 22872754:177:138
status: NEW