Regulation of Class A scavenger receptor-mediated cell adhesion and surface localization by PI3K: identification of a regulatory cytoplasmic motif
Regulation of Class A scavenger receptor-mediated cell adhesion and surface localization by PI3K: identification of a regulatory cytoplasmic motif
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DOI：
10.1189/jlb.0509318
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发表时间：
2010-03-01
影响因子：
5.5
通讯作者：
Post, Steven R.
中科院分区：
文献类型：
--
作者：
Cholewa, Jill;Nikolic, Dejan;Post, Steven R.
细胞质基序在差异调节SR-A功能中的重要性通过删除前49个细胞质aa （SR-A(Delta 1-49)）来证明，这消除了SR-A介导的配体内化而不降低细胞粘附。为了鉴定前49个aa内调节SR-A功能的其他细胞质基序，将保守基序（EDAD）中的酸性残基改变为其酰胺衍生物（SR-A(QNAN)）。比较SR-A（QNAN）与SR-A（Delta 1-49）和SR-A在转染HEK-293细胞中的功能和调控。阻断PI3K激活可抑制SR-A，但不抑制SR-A(Delta 1-49)-或SR-A（QNAN）介导的细胞粘附。虽然删除（SR-A(Delta 1-49)）或突变（SR-A(QNAN)） EDAD基序会消除PI3K对SR-A介导的细胞粘附的敏感性，但这些突变不会影响配体内化或细胞粘附过程中PI3K的激活。为了明确PI3K调控SR-A介导的细胞粘附的机制，我们检测了野生型和突变型SR-A的细胞定位。PI3K抑制降低了SR-A的表面定位，但没有降低SRA（Delta 1-49）或SR-A（QNAN）的表面定位。在内源性表达SR-A的腹膜巨噬细胞中证实了PI3K对SR-A表面定位的调控。总之，这些结果表明SR-A与固定配体结合激活PI3K以募集更多受体到质膜并增强细胞粘附的途径。j . Leukoc。生物学报87:443-449；2010.
The importance of cytoplasmic motifs in differentially regulating SR-A function was demonstrated by deleting the first 49 cytoplasmic aa (SR-A(Delta 1-49)), which abolished SR-A-mediated ligand internalization without reducing cell adhesion. To identify additional cytoplasmic motifs within the first 49 aa that regulate SR-A function, the acidic residues in a conserved motif (EDAD) were changed to their amide derivatives (SR-A(QNAN)). The function and regulation of SR-A(QNAN) were compared with that of SR-A(Delta 1-49) and SR-A in transfected HEK-293 cells. Blocking PI3K activation inhibited SR-A, but not SR-A(Delta 1-49)- or SR-A(QNAN)-mediated cell adhesion. Although deleting (SR-A(Delta 1-49)) or mutating (SR-A(QNAN)) the EDAD motif abolished the PI3K sensitivity of SR-A-mediated cell adhesion, these mutations did not affect ligand internalization or PI3K activation during cell adhesion. To define the mechanism by which PI3K regulates SR-A-mediated cell adhesion, the cellular localization of wild-type and mutant SR-A was examined. PI3K inhibition reduced surface localization of SR-A but not of SRA(Delta 1-49) or SR-A(QNAN). The regulation of SR-A surface localization by PI3K was confirmed in peritoneal macrophages, which endogenously express SR-A. Together, these results suggest a pathway in which SR-A binding to an immobilized ligand activates PI3K to recruit more receptor to the plasma membrane and enhances cell adhesion. J. Leukoc. Biol. 87: 443-449; 2010.