ANALYSIS OF CD36 BINDING DOMAINS - LIGAND SPECIFICITY CONTROLLED BY DEPHOSPHORYLATION OF AN ECTODOMAIN
ANALYSIS OF CD36 BINDING DOMAINS - LIGAND SPECIFICITY CONTROLLED BY DEPHOSPHORYLATION OF AN ECTODOMAIN
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DOI：
10.1126/science.7504322
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发表时间：
1993-11-26
期刊：
影响因子：
56.9
通讯作者：
PERNAMBUCO, M
中科院分区：
文献类型：
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作者：
ASCH, AS;LIU, I;PERNAMBUCO, M
蛋白质CD 36是血小板反应蛋白（TSP）、疟疾感染的红细胞和胶原蛋白的膜受体。在CD 36的单个二硫环内鉴定了三个功能序列：一个介导TSP结合（氨基酸87至99），两个支持疟疾细胞粘附（氨基酸8至21和97至110）。这些肽之一（p87-99）是共有蛋白激酶C（PKC）磷酸化位点。静息血小板和巨核细胞系中组成性磷酸化CD 36的去磷酸化导致胶原蛋白粘附和血小板对胶原蛋白的反应性丧失，TSP结合力相应增加。PKC介导的磷酸化的胞外域导致TSP结合的损失和胶原结合的相互收购。 在定点突变研究中，当苏氨酸磷酸化位点改变为丙氨酸时，CD 36以去磷酸化状态表达，并组成性地与TSP结合。
The protein CD36 is a membrane receptor for thrombospondin (TSP), malaria-infected erythrocytes, and collagen. Three functional sequences were identified within a single disulfide loop of CD36: one that mediates TSP binding (amino acids 87 to 99) and two that support malarial cytoadhesion (amino acids 8 to 21 and 97 to 110). One of these peptides (p87-99) is a consensus protein kinase C (PKC) phosphorylation site. Dephosphorylation of constitutively phosphorylated CD36 in resting platelets and a megakaryocytic cell line led to the loss of collagen adhesion and platelet reactivity to collagen, with a reciprocal increase in TSP binding. PKC-mediated phosphorylation of this ectodomain resulted in a loss of TSP binding and the reciprocal acquisition of collagen binding. In site-directed mutagenesis studies, when the threonine phosphorylation site was changed to alanine, CD36 was expressed in a dephosphorylated state and bound to TSP constitutively.