ABCA1 p.Tyr924Phe
| Predicted by SNAP2: | A: D (71%), C: D (71%), D: D (85%), E: D (85%), F: D (53%), G: D (80%), H: D (66%), I: D (66%), K: D (85%), L: D (75%), M: D (80%), N: D (85%), P: D (85%), Q: D (80%), R: D (85%), S: D (80%), T: D (85%), V: D (71%), W: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, |
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[hide] The macrophage cholesterol exporter ABCA1 function... J Biol Chem. 2009 Nov 20;284(47):32336-43. Epub 2009 Sep 25. Tang C, Liu Y, Kessler PS, Vaughan AM, Oram JF
The macrophage cholesterol exporter ABCA1 functions as an anti-inflammatory receptor.
J Biol Chem. 2009 Nov 20;284(47):32336-43. Epub 2009 Sep 25., [PMID:19783654]
Abstract [show]
ATP-binding cassette transporter A1 (ABCA1) is a cell membrane protein that exports excess cholesterol from cells to apolipoprotein (apo) A-I, the major protein in high density lipoproteins. Genetic studies have shown that ABCA1 protects against cardiovascular disease. The interaction of apoA-I with ABCA1 promotes cholesterol removal and activates signaling molecules, such as Janus kinase 2 (JAK2), that optimize the lipid export activity of ABCA1. Here we show that the ABCA1-mediated activation of JAK2 also activates STAT3, which is independent of the lipid transport function of ABCA1. ABCA1 contains two candidate STAT3 docking sites that are required for the apoA-I/ABCA1/JAK2 activation of STAT3. The interaction of apoA-I with ABCA1-expressing macrophages suppressed the ability of lysopolysaccaride to induce the inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, which was reversed by silencing STAT3 or ABCA1. Thus, the apoA-I/ABCA1 pathway in macrophages functions as an anti-inflammatory receptor through activation of JAK2/STAT3. These findings implicate ABCA1 as a direct molecular link between the cardioprotective effects of cholesterol export from arterial macrophages and suppressed inflammation.
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No. Sentence Comment
42 Cells were selected against Neozi, and clonal lines expressing similar amounts of wild-type (WT) ABCA1, mutants Y924F, Y1990F, or Y924/1990F were used for the experiments.
X
ABCA1 p.Tyr924Phe 19783654:42:112
status: NEW112 Probing immunoprecipitates of STAT3 with an ABCA1 antibody revealed that the apoA-I-stimulated interaction of ABCA1 with STAT3 was completely abolished by the Y924F/ Y1990F mutations (Fig. 3C).
X
ABCA1 p.Tyr924Phe 19783654:112:24
status: NEWX
ABCA1 p.Tyr924Phe 19783654:112:159
status: NEW114 A lack of effect of the Y924F and Y1990F mutations on cholesterol efflux despite a loss of STAT3 phosphorylation (Fig. 3, A and B) indicates that the ABCA1-dependent activation of STAT3 plays no role in the cholesterol export function of ABCA1.
X
ABCA1 p.Tyr924Phe 19783654:114:24
status: NEW128 A, mifepristone-treated BHK cells transfected with wild-type (WT) ABCA1 or ABCA1 containing Y924F, Y1990F, or Y924F/Y1990F substitutions were labeled with [3 H]cholesterol and incubated for 2 h without or with 10 g/ml apoA-I, and cholesterol efflux was calculated as the apoA-I-mediated release of [3 H]cholesterol into the medium normalized for values for WT cells.
X
ABCA1 p.Tyr924Phe 19783654:128:92
status: NEWX
ABCA1 p.Tyr924Phe 19783654:128:110
status: NEW133 C, whole cell lysates from BHK cells transfected with WT and Y924F/Y1990F were immunoprecipitated with anti-STAT3 antibody and immunoblotted with anti-ABCA1 antibody.
X
ABCA1 p.Tyr924Phe 19783654:133:61
status: NEW41 Cells were selected against Neozi, and clonal lines expressing similar amounts of wild-type (WT) ABCA1, mutants Y924F, Y1990F, or Y924/1990F were used for the experiments.
X
ABCA1 p.Tyr924Phe 19783654:41:112
status: NEW110 Probing immunoprecipitates of STAT3 with an ABCA1 antibody revealed that the apoA-I-stimulated interaction of ABCA1 with STAT3 was completely abolished by the Y924F/ Y1990F mutations (Fig. 3C).
X
ABCA1 p.Tyr924Phe 19783654:110:159
status: NEW126 A, mifepristone-treated BHK cells transfected with wild-type (WT) ABCA1 or ABCA1 containing Y924F, Y1990F, or Y924F/Y1990F substitutions were labeled with [3 H]cholesterol and incubated for 2 h without or with 10 òe;g/ml apoA-I, and cholesterol efflux was calculated as the apoA-I-mediated release of [3 H]cholesterol into the medium normalized for values for WT cells.
X
ABCA1 p.Tyr924Phe 19783654:126:92
status: NEWX
ABCA1 p.Tyr924Phe 19783654:126:110
status: NEW131 C, whole cell lysates from BHK cells transfected with WT and Y924F/Y1990F were immunoprecipitated with anti-STAT3 antibody and immunoblotted with anti-ABCA1 antibody.
X
ABCA1 p.Tyr924Phe 19783654:131:61
status: NEW