Fibronectin and heparin binding domains of latent TGF-β binding protein (LTBP)-4 mediate matrix targeting and cell adhesion

被引:61
作者
Kantola, Anna K.
Keski-Oja, Jorma
Koli, Katri
机构
[1] Univ Helsinki, Haartman Inst, Dept Virol, FIN-00014 Helsinki, Finland
[2] Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland
[3] Helsinki Univ Hosp, Helsinki 00014, Finland
基金
芬兰科学院;
关键词
LTBP; TGF-beta; fibronectin; ECM; cell adhesion;
D O I
10.1016/j.yexcr.2008.05.010
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Latent transforming growth factor (TGF)-beta binding proteins are extracellular matrix (ECM) proteins involved in the regulation of TGF-beta sequestration and activation. In this study, we have identified binding domains in LTBP-4, which mediate matrix targeting and cell adhesion. LTBP-4 was found to possess heparin binding activity, especially in its N-terminal region. The C-terminal domain of LTBP-4 supported fibroblast adhesion, a property reduced by soluble heparin. In addition, we found that LTBP-4 binds directly to fibronectin (FN), which was indispensable for the matrix assembly of LTBP-4. The FN binding sites were also located in the N-terminal region. Interestingly, heparin was able to reduce the binding of LTBP-4 to FN. In fibroblast cultures, LTBP-4 colocalized first with FN and subsequently with fibrillin-1, pointing to a role for FN in the early assembly of LTBP-4. In FN-/- fibroblasts, LTBP-mediated ECM targeting was disturbed, resulting in increased TGF-beta activity. These results revealed new molecular interactions which are evidently important for the ECM targeting, but which also are evidence of novel functions for LTBP-4 as an adhesion molecule. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:2488 / 2500
页数:13
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