The Simpson-Golabi-Behmel syndrome causative Glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26
The Simpson-Golabi-Behmel syndrome causative Glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26
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DOI：
10.1002/pmic.200600654
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发表时间：
2007-06-01
期刊：
影响因子：
3.4
通讯作者：
MacKenzie, Alex E.
中科院分区：
文献类型：
--
作者：
Davoodi, Jamshid;Kelly, John;MacKenzie, Alex E.
辛普森-戈拉比-贝梅尔综合征（SGBS）是一种x连锁疾病，被证明是glypican-3 （GPC3）基因缺失的结果。GPC3是一种通过糖基磷脂酰肌醇（GPI）锚定定位于细胞膜的蛋白多糖。为了进一步阐明GPC3的功能，我们筛选了多种细胞系，寻找与GPC3相互作用的蛋白，最终分离出一个115 kDa的蛋白，被鉴定为CD26。这种相互作用发生在GPC3的糖基化和非糖基化形式，并导致CD26肽酶活性的抑制。此外，在Cos-1细胞中引入CD26会导致细胞生长的上调，而在培养基中加入重组GPC3会显著降低转染CD26的Cos-1细胞的生长。此外，含有CD26的HepG2 C3A细胞在重组GPC3存在下发生了浓度依赖性和时间依赖性的凋亡。鉴于抑制CD26会降低细胞增殖速率，我们提出在SGBS患者中观察到的一些物理结果可能是GPC3与CD26直接相互作用的结果。此外，没有GPI锚点的GPC3能够诱导细胞凋亡，这表明诱导细胞凋亡既不需要GPI锚点，也不需要膜附着。
Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked condition shown to be the result of deletions of the glypican-3 (GPC3) gene. GPC3 is a proteoglycan localized to the cell membrane via a glycosylphosphatidyl-inositol (GPI) anchor. To further elucidate the GPC3 function(s), we have screened various cell lines for proteins that interact with GPC3, resulting in the isolation of a 115 kDa protein, identified as CD26. The interaction occurred with both the glycosylated and unglycosylated forms of GPC3 and led to the inhibition of CD26 peptidase activity. Moreover, introduction of CD26 into Cos-1 cells was accompanied by the up-regulation of cell growth, while inclusion of recombinant GPC3 in the media reduced the growth of CD26 transfected Cos-1 cells, drastically. Furthermore, HepG2 C3A cells containing CD26 underwent apoptosis in the presence of recombinant GPC3 in both concentration and time-dependant manner. in light of the fact that inhibition of CD26 reduces the rate of cell proliferation, we propose that a number of physical findings observed in SGBS patients maybe a consequence of a direct interaction of GPC3 with CD26. Furthermore, GPC3 without the GPI anchor is capable of inducing apoptosis indicating that neither the GPI anchor nor the membrane attachment is required for apoptosis induction.