Fibronectin type III5 repeat contains a novel cell adhesion sequence, KLDAPT, which binds activated alpha 4 beta 1 and alpha 4 beta 7 integrins
Fibronectin type III5 repeat contains a novel cell adhesion sequence, KLDAPT, which binds activated alpha 4 beta 1 and alpha 4 beta 7 integrins
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DOI：
10.1074/jbc.272.40.24832
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发表时间：
1997-10-03
影响因子：
4.8
通讯作者：
GarciaPardo, A
中科院分区：
文献类型：
--
作者：
Moyano, JV;Carnemolla, B;GarciaPardo, A
纤维连接蛋白包含III型重复序列4-6的区域含有一个低亲和力的肝素结合域，但其生理意义尚不清楚，我们已经研究了该区域是否能够像其他纤维连接蛋白的肝素结合域那样与细胞相互作用，计算机搜索发现位于FN-III5的KLDAPT序列，含有该序列的合成肽在激活的抗β1单抗TS2/16或与Mn2+作用时诱导淋巴细胞黏附，表明KLDAPT与整合素结合。含有重复序列III5的重组片段(FN-III5)也能介导TS2/16/Mn2+处理的细胞的黏附，而FN-III6片段不能，可溶性KLDAPT多肽抑制细胞与FN-III5以及38 kDa的纤维连接蛋白片段和VCAM-1的黏附，KLDAPT是已知的α4β1整合素的两个配体，KLDAPT还与可溶性碱性磷酸酶偶联的VCAM-Ig与Mn2+处理的α4β1竞争结合。此外，单抗反α4和抗α4β7，而不是单抗抑制细胞与FN-II5和KLDAPT，KLDAPT，因此，这些结果建立了FN-III5重复序列的细胞黏附功能，并表明KLDAPT是一种新的激活的α4整合素的纤维连接蛋白配体。
The region of fibronectin encompassing type III repeats 4-6 contains a low affinity heparin binding domain, but its physiological significance is not clear, We have studied whether this domain is able to interact with cells as already shown for other heparin binding domains of fibronectin, A computer search based on homologies with known active sites in fibronectin revealed the sequence KLDAPT located in FN-III5, A synthetic peptide containing this sequence induced lymphoid cell adhesion upon treatment with the activating anti-beta 1 monoclonal antibody (mAb) TS2/16 or with Mn2+ indicating that KLDAPT was binding to an integrin, A recombinant fragment containing repeat III5 (FN-III5) also mediated adhesion of TS2/16/Mn2+-treated cells while the FN-III6 fragment did not, Soluble KLDAPT peptide inhibited cell adhesion to FN-III5 as well as to a 38-kDa fibronectin fragment and VCAM-1, two previously known ligands for alpha 4 beta 1 integrin, KLDAPT also competed with the binding of soluble alkaline phosphatase-coupled VCAM-Ig to Mn2+-treated alpha 4 beta 1. Furthermore, mAbs anti-alpha 4 and anti-alpha 4 beta 7, but not mAbs to other integrins, inhibited cell adhesion to FN-III5 and KLDAPT, These results therefore establish a cell adhesive function for the FN-III5 repeat and show that KLDAPT is a novel fibronectin ligand for activated alpha 4 integrins.