A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis
A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis
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DOI：
10.1074/jbc.m303424200
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发表时间：
2003-07-04
影响因子：
4.8
通讯作者：
Pauli, BU
中科院分区：
文献类型：
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作者：
Cheng, HC;Abdel-Ghany, M;Pauli, BU
肺内皮二肽基肽酶IV（DPPIV/CD 26）是一种以细胞表面多聚纤连蛋白（poly-FN）修饰的癌细胞的血管定位。在这里，我们确定了FN中的DPPIV结合位点，并研究了结合位点肽对DPPIV/聚FN粘附和转移的影响。使用共同跨越全长FN的蛋白水解片段和麦芽糖结合蛋白融合蛋白，我们在III型重复序列13、14和15（分别为FNIII 13、-14和-15）中发现了DPPIV结合位点。DPPIV结合由共有基序T（I/L）TGLX（P/R）G（T/V）X介导，并通过将FNIII 13、-14和-15中的该基序与FNIII 12中不结合DPPIV的相应区域交换来证实。DPPIV结合在交换的FNIII 13、-14和-15中丢失，在交换的FNIII 12中获得（FNIII 12（14））。含有FNIII 14的DPPIV结合结构域的肽阻断DPPIV/聚FN粘附并阻止肺转移。这项研究增加了FN的细胞表面粘附受体的类别，并将有助于进一步表征DPPIV/聚FN粘附在转移中的功能意义，并可能在涉及DPPIV表达淋巴细胞的细胞介导的免疫中。
Lung endothelial dipeptidyl peptidase IV (DPPIV/CD26) is a vascular address for cancer cells decorated with cell-surface polymeric fibronectin (poly-FN). Here, we identified the DPPIV-binding sites in FN and examined the effect of binding site peptides on DPPIV/poly-FN adhesion and metastasis. Using proteolytic fragments and maltose-binding protein fusion proteins that together span full-length FN, we found DPPIV-binding sites in type III repeats 13, 14, and 15 (FNIII13, -14, and -15, respectively). DPPIV binding was mediated by the consensus motif T(I/L)TGLX(P/R)G(T/V)X and was confirmed by swapping this motif in FNIII13, -14, and -15 with the corresponding region in FNIII12, which did not bind DPPIV. DPPIV binding was lost in swapped FNIII13, -14, and -15 and gained in swapped FNIII12 ( FNIII12( 14)). Peptides containing the DPPIV-binding domain of FNIII14 blocked DPPIV/poly-FN adhesion and impeded pulmonary metastasis. This study adds to the classes of cell-surface adhesion receptors for FN and will help in the further characterization of the functional implications of the DPPIV/poly-FN adhesion in metastasis and possibly in cell-mediated immunity involving DPPIV-expressing lymphocytes.