The heparin binding domain of vitronectin is the region that is required to enhance insulin-like growth factor-I signaling

被引：31

作者：

Maile, LA ^{[1
]}

Busby, WH ^{[1
]}

Sitko, K ^{[1
]}

Capps, BE ^{[1
]}

Sergent, T ^{[1
]}

Badley-Clarke, J ^{[1
]}

Ling, Y ^{[1
]}

Clemmons, DR ^{[1
]}

机构：

[1] Univ N Carolina, Div Endocrinol, Chapel Hill, NC 27599 USA

来源：

MOLECULAR ENDOCRINOLOGY | 2006年 / 20卷 / 04期

关键词：

D O I：

10.1210/me.2005-0382

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We have shown that vitronectin (Vn) binding to a cysteine loop sequence within the extracellular domain of the beta 3-subunit ( amino acids 177 - 184) of alpha V beta 3 is required for the positive effects of Vn on IGF-I signaling. When Vn binding to this sequence is blocked, IGF-I signaling in smooth muscle cells is impaired. Because this binding site is distinct from the site on beta 3 to which the Arg-Gly-Asp sequence of extracellular matrix ligands bind ( amino acids 107 - 171), we hypothesized that the region of Vn that binds to the cysteine loop on beta 3 is distinct from the region that contains the Arg-Gly-Asp sequence. The results presented in this study demonstrate that this heparin binding domain (HBD) is the region of Vn that binds to the cysteine loop region of beta 3 and that this region is sufficient to mediate the positive effects of Vn on IGF-I signaling. We provide evidence that binding of the HBD of Vn to alpha V beta 3 has direct effects on the activation state of beta 3 as measured by beta 3 phosphorylation. The increase in beta 3 phosphorylation associated with exposure of cells to this HBD is associated with enhanced phosphorylation of the adaptor protein Src homology 2 domain-containing transforming protein C and enhanced activation MAPK, a downstream mediator of IGF-I signaling. We conclude that the interaction of the HBD of Vn binding to the cysteine loop sequence of beta 3 is necessary and sufficient for the positive effects of Vn on IGF-I-mediated effects in smooth muscle cells.

引用

页码：881 / 892

页数：12

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