MECHANISMS OF PROTEOGLYCAN/COLLAGEN INTERACTIONS

蛋白聚糖/胶原蛋白相互作用的机制

• 批准号: 6184067
• 负责人: James D SanAntonio
• 金额: $ 11.34万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6184067
• 关键词: chemical binding; collagen; electrophoresis; intermolecular interaction; laboratory rat; molecular site; protein structure function; proteoglycan; recombinant proteins

Proteoglycan-collagen interactions are ubiquitous in most vertebrate tissues and likely play key roles in cell adhesion, migration, and extracellular matrix (ECM)assembly and function. Although the biochemistry of the binding between the cell surface or secreted proteoglycans and collagens is incompletely understood, a primarily electrostatic, non-specific basis for their interactions has been proposed. However, by electron microscopy this laboratory has observed heparin binding to specific regions on type I collagen monomers and fibrils, and using affinity coelectrophoresis has shown that high affinity collagen-binding domains comprise only a small fraction of the heparin molecule. These results favor the hypothesis that high affinity heparin-type I collagen binding depends more upon unique, sparsely represented domains or sequences within the glycosaminoglycan and protein, than upon site-independent electrostatic interactions. To test the above hypothesis, first, the collagen-binding sites of heparin will be isolated and their abundance, size, sequence, and binding selectivity for other ECM molecules will be determined by affinity coelectrophoresis (ACE) and other biochemical approaches. Second, the putative heparin-binding regions of type I collagen will be confirmed by studying the interactions of heparin with a) recombinant type I collagens in which D-period segments have either been deleted or inserted in multiple copies, or in altered positions, and b) with "mini collagen" peptides carrying known type I collagen sequences. Last, the identified interactive domains of heparin and type I collagen will be tested in cell interactions with type i collagen and with other ECM molecules. These studies will define the biochemistry and function of one of the most abundant of cell-matrix interactions, and contribute to the understanding and treatment of diseases such as cancer which involve abnormal cell adhesion and migration within the ECM.

蛋白聚糖-胶原相互作用在大多数脊椎动物中普遍存在 组织，并可能在细胞粘附，迁移和 细胞外基质（ECM）组装和功能。虽然 细胞表面或分泌的 蛋白聚糖和胶原蛋白的研究还不完全清楚， 静电，非特定的基础上，他们的相互作用已被 提出了然而，通过电子显微镜，这个实验室 观察到肝素与I型胶原蛋白上的特定区域结合 单体和原纤维，并使用亲和共电泳显示， 高亲和力胶原蛋白结合结构域仅包含小的 肝素分子的一部分。这些结果支持假设 高亲和力肝素-I型胶原结合更多地依赖于 独特的，稀疏表示的结构域或序列内的 糖胺聚糖和蛋白质，而不是位点非依赖性 静电相互作用 为了检验上述假设，首先， 肝素将被分离，并且它们的丰度、大小、序列和 对其它ECM分子的结合选择性将通过以下测定： 亲和共电泳（ACE）和其他生物化学方法。 第二，I型胶原蛋白的假定肝素结合区域将 通过研究肝素与a） 重组I型胶原，其中D期区段具有 在多个拷贝中被删除或插入，或在改变的位置， 和B）携带已知I型胶原的“迷你胶原”肽 序列的最后，确定了肝素和 I型胶原将在与I型胶原的细胞相互作用中进行测试 和其他ECM分子。这些研究将确定 最丰富的细胞基质之一的生物化学和功能 相互作用，并有助于理解和治疗 涉及异常细胞粘附的疾病如癌症， 在ECM中迁移。

项目成果

Heparan sulfate proteoglycans: a GAGgle of skeletal-hematopoietic regulators.

• DOI: 10.1002/dvdy.21593
• 发表时间: 2008-10
• 期刊: DEVELOPMENTAL DYNAMICS
• 影响因子: 2.5
• 作者: Rodgers, Kathryn D.;Antonio, James D. San;Jacenko, Olena
• 通讯作者: Jacenko, Olena

Non-enzymatic glycation of type I collagen diminishes collagen-proteoglycan binding and weakens cell adhesion.

• DOI: 10.1002/jcb.21735
• 发表时间: 2008-08-01
• 期刊: JOURNAL OF CELLULAR BIOCHEMISTRY
• 影响因子: 4
• 作者: Reigle, Kristin L.;Di Lullo, Gloria;Turner, Kevin R.;Last, Jerold A.;Chervoneva, Inna;Birk, David E.;Funderburgh, James L.;Elrod, Elizabeth;Germann, Markus W.;Surber, Charles;Sanderson, Ralph D.;Antonio, James D. San
• 通讯作者: Antonio, James D. San

Insulin-like growth factor (IGF) binding protein-3 regulation of IGF-I is altered in an acidic extracellular environment.

胰岛素样生长因子 (IGF) 结合蛋白 3 对 IGF-I 的调节在酸性细胞外环境中发生改变。

• DOI: 10.1002/jcp.10033
• 发表时间: 2001
• 期刊: Journal of cellular physiology.
• 作者: Forsten,KE;Akers,RM;SanAntonio,JD
• 通讯作者: SanAntonio,JD