The potential of laminin-2-biomimetic short peptide to promote cell adhesion, spreading and migration by inducing membrane recruitment and phosphorylation of PKCδ
The potential of laminin-2-biomimetic short peptide to promote cell adhesion, spreading and migration by inducing membrane recruitment and phosphorylation of PKCδ
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DOI：
10.1016/j.biomaterials.2012.02.002
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发表时间：
2012-05-01
期刊：
影响因子：
14
通讯作者：
Min, Byung-Moo
中科院分区：
文献类型：
--
作者：
Jung, Sung Youn;Kim, Jin-Man;Min, Byung-Moo
层粘连蛋白α2链在基底膜组装和外周髓鞘形成中发挥重要作用；然而，人们对人层粘连蛋白α2链内的整合素结合基序以及该配体受体相互作用下游的信号传导途径知之甚少。我们在人层粘连蛋白 α 2 链的 LG3 结构域内鉴定了一个基序 RNIPPFEGCIWN (Ln2-LG3-P2)，作为 α 3 β 1 整联蛋白和细胞活动（如细胞粘附、扩散和迁移）的主要位点。 α3β1 整合素与 Ln2-LG3-P2 的结合诱导蛋白激酶 CS (PKCS) 的膜募集并刺激其酪氨酸磷酸化。 Ln2-LG3-P2 诱导的细胞活性和粘着斑激酶 (FAK) 磷酸化可被 PKC δ 抑制剂 Rottlerin 抑制，但不能被 PKC α/β 抑制剂 Go6976 抑制。这些结果表明人层粘连蛋白α2链内的RNIPPFEGCIWN基序是α3β1整联蛋白的主要配体，并且α3β1整联蛋白的结合通过膜募集和PKCδ的酪氨酸磷酸化和FAK磷酸化介导细胞活性。 (C) 2012 Elsevier Ltd. 保留所有权利。
Laminin alpha 2 chain plays an important role in basement membrane assembly and peripheral myelinogenesis; however, the integrin binding motif within human laminin alpha 2 chain and the signaling pathways downstream of this ligand receptor interaction are poorly understood. We identified a motif, RNIPPFEGCIWN (Ln2-LG3-P2), within LG3 domain of human laminin alpha 2 chain as a major site for both alpha 3 beta 1 integrin and cellular activities such as cell adhesion, spreading, and migration. Binding of alpha 3 beta 1 integrin with Ln2-LG3-P2 induced the membrane recruitment of protein kinase CS (PKCS) and stimulated its tyrosine phosphorylation. The cellular activities induced by Ln2-LG3-P2 and the phosphorylation of focal adhesion kinase (FAK) were inhibited by rottlerin, a PKC delta inhibitor, but not by Go6976, a PKC alpha/beta inhibitor. These results indicate that RNIPPFEGCIWN motif within human laminin alpha 2 chain is a major ligand for alpha 3 beta 1 integrin, and that binding of alpha 3 beta 1 integrin mediates cellular activities through membrane recruitment and tyrosine phosphorylation of PKC delta and FAK phosphorylation. (C) 2012 Elsevier Ltd. All rights reserved.