ABCMdb

ABCG1 p.Ser388Ala

Predicted by SNAP2:	A: N (78%), C: N (66%), D: N (66%), E: N (82%), F: D (66%), G: N (72%), H: N (72%), I: N (61%), K: N (87%), L: N (66%), M: N (66%), N: N (87%), P: N (82%), Q: N (82%), R: N (78%), T: N (93%), V: N (72%), W: D (71%), Y: D (66%),
Predicted by PROVEAN:	A: N, C: N, D: N, E: N, F: N, 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: N,

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Publications
[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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Sentences [show]
No. Sentence Comment
139 HDL-induced cholesterol export from cells expressing ABCG1(+12)-S388A and ABCG1(+12)- S390A was similar to that of cholesterol export from wild-type ABCG1(+12) cells (Fig. 4). Login to comment
140 Furthermore, upon incubation with H89, cholesterol export from cells expressing the S388A or S390A mutants was increased to a level similar to that of the parental ABCG1(+12). Login to comment
177 H89 significantly increased cholesterol export from cells expressing ABCG1(+12), S388A, and S390A (P < 0.05), but not ABCG1(afa;12) or S389A. Login to comment