Adhesive and migratory effects of phosphophoryn are modulated by flanking peptides of the integrin binding motif.
Adhesive and migratory effects of phosphophoryn are modulated by flanking peptides of the integrin binding motif.
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DOI：
10.1371/journal.pone.0112490
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nishimura F
中科院分区：
文献类型：
--
作者：
Suzuki S;Kobuke S;Haruyama N;Hoshino H;Kulkarni AB;Nishimura F
磷酸蛋白（PP）是由牙本质唾液磷蛋白（DSPP）的蛋白水解切割产生的。在有齿动物中，祖先牙本质基质蛋白-1（dentin matrix protein-1，DSPP-1）基因组序列中的基因重复产生了DSPP基因。PP和β-l是磷酸化的细胞外基质蛋白，其属于小整联蛋白结合配体N-连接糖蛋白（SIBLING）家族。许多SIBLING成员已被证明通过整合素结合Arg-Gly-Asp（RGD）结构域引起各种细胞反应;然而，PP的RGD依赖性功能尚未完全了解。我们证明，重组PP没有表现出任何明显的细胞粘附能力，而同时纯化的重组PP-I则表现出明显的细胞粘附能力。通过在接种到玻连蛋白上之前将人骨肉瘤MG 63细胞与各种PP肽预孵育来进行细胞粘附抑制分析。结果表明，在PP-RGD结构域的两侧掺入一个以上的氨基酸不能抑制MG 63细胞与玻连蛋白的粘附。此外，含有羧基端开放的PP-RGD结构域的肽（H-463 SDESDTNSESANESGSRGDA 482-OH）的抑制活性比含有氨基端开放的RGD结构域的肽（H-478 SRGDASYTSDESSDDDDNDSDSH 499-OH）的抑制活性更强。这种现象得到了支持的重组截短PP，其终止与Ala 482的有效的细胞粘附和迁移能力。此外，Ala 482和/或Ser 483中的各种点突变将重组PP转化为细胞粘附蛋白。因此，我们得出结论，在灵长类动物和小鼠中检测到的Ala 482-Ser 483侧翼序列是允许PP-RGD结构域被隔离的关键肽键。PP和DSPP-1作用于整合素的不同能力意味着DSPP是从DSPP-1复制而来，作为牙齿发育的关键细胞外蛋白，而不是作为整合素介导的信号分子。
Phosphophoryn (PP) is generated from the proteolytic cleavage of dentin sialophosphoprotein (DSPP). Gene duplications in the ancestor dentin matrix protein-1 (DMP-1) genomic sequence created the DSPP gene in toothed animals. PP and DMP-1 are phosphorylated extracellular matrix proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Many SIBLING members have been shown to evoke various cell responses through the integrin-binding Arg-Gly-Asp (RGD) domain; however, the RGD-dependent function of PP is not yet fully understood. We demonstrated that recombinant PP did not exhibit any obvious cell adhesion ability, whereas the simultaneously purified recombinant DMP-1 did. A cell adhesion inhibitory analysis was performed by pre-incubating human osteosarcoma MG63 cells with various PP peptides before seeding onto vitronectin. The results obtained revealed that the incorporation of more than one amino acid on both sides of the PP-RGD domain was unable to inhibit the adhesion of MG63 cells onto vitronectin. Furthermore, the inhibitory activity of a peptide containing the PP-RGD domain with an open carboxyl-terminal side (H-463SDESDTNSESANESGSRGDA482-OH) was more potent than that of a peptide containing the RGD domain with an open amino-terminal side (H-478SRGDASYTSDESSDDDNDSDSH499-OH). This phenomenon was supported by the potent cell adhesion and migration abilities of the recombinant truncated PP, which terminated with Ala482. Furthermore, various point mutations in Ala482 and/or Ser483 converted recombinant PP into cell-adhesive proteins. Therefore, we concluded that the Ala482-Ser483 flanking sequence, which was detected in primates and mice, was the key peptide bond that allowed the PP-RGD domain to be sequestered. The differential abilities of PP and DMP-1 to act on integrin imply that DSPP was duplicated from DMP-1 to serve as a crucial extracellular protein for tooth development rather than as an integrin-mediated signaling molecule.
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影响因子：
6.2
作者：
Deshpande, Atul Suresh;Fang, Ping-An;Zhang, Xiaoyuan;Jayaraman, Thottala;Sfeir, Charles;Beniash, Elia
通讯作者：
Beniash, Elia
影响因子：
2.9
作者：
Qin, CL;Brunn, JC;Butler, WT
通讯作者：
Butler, WT
影响因子：
4.8
作者：
Christensen, Brian;Schack, Lotte;Sorensen, Esben S.
通讯作者：
Sorensen, Esben S.
影响因子：
2.9
作者：
Fisher, LW;Fedarko, NS
通讯作者：
Fedarko, NS
牙本质唾液酸磷蛋白 (DSPP) 基因沉默可抑制人口腔癌细胞系 OSC2 的关键致瘤活性。
影响因子：
3.7
作者：
Joshi R;Tawfik A;Edeh N;McCloud V;Looney S;Lewis J;Hsu S;Ogbureke KU
通讯作者：
Ogbureke KU