PINCH: More than just an adaptor protein in cellular response.
PINCH: More than just an adaptor protein in cellular response.
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DOI：
10.1002/jcp.22437
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发表时间：
2011-04
影响因子：
5.6
通讯作者：
Langford, Dianne
中科院分区：
文献类型：
--
作者：
Kovalevich, Jane;Tracy, Brittany;Langford, Dianne
特别有趣的新型富含半胱氨酸-组氨酸的蛋白 (PINCH) 是一种仅包含 LIM 结构域的衔接蛋白，参与蛋白募集、多蛋白复合物的后续组装以及这些复合物的亚细胞定位。 PINCH 受发育调节，其表达对于正确的细胞骨架组织和细胞外基质粘附至关重要。尽管 PINCH 没有催化能力，但 PIP (PINCH-ILK-parvin) 复合物充当整合素与生长因子受体激酶和 GTP 信号通路成分之间的联系。因此，PINCH 介导的信号传导诱导细胞迁移、扩散和存活。对 PINCH 影响的信号级联的进一步研究是理解其在细胞命运和系统维护中的生物学意义的关键，因为 PINCH 的发育功能可能延伸到疾病状态和细胞对损伤的反应。 PINCH 与多种疾病有关，包括肾衰竭、心肌病、神经系统变性和脱髓鞘以及肿瘤发生。本综述提供了 PINCH 在正常细胞过程和发病机制中结构和功能重要性的证据。目前关于 PINCH 在神经系统疾病中表达的数据是大量的，但由于这种蛋白质的复杂性和普遍性，我们对其病理学功能的理解仍不清楚。在这篇综述中，将讨论识别 PINCH 结合伴侣、它们的分子相互作用以及 PINCH 在癌症和神经系统疾病中潜在重叠作用的研究概述。关于 PINCH 在细胞中的作用仍然存在许多问题。是什么诱导细胞特异性 PINCH 表达？ PINCH 表达如何影响中枢神经系统的细胞命运？更广泛地说，疾病中的 PINCH 表达是一件好事吗？澄清中枢神经系统和其他系统中 PINCH 表达的模糊功能对于更清楚地了解健康和疾病中的信号事件非常重要。
Particularly interesting new cysteine-histidine-rich protein (PINCH) is a LIM-domain-only adaptor protein involved in protein recruitment, subsequent assembly of multi-protein complexes, and subcellular localization of these complexes. PINCH is developmentally regulated and its expression is critical for proper cytoskeletal organization and extracellular matrix adhesion. Although PINCH has no catalytic abilities, the PIP (PINCH–ILK–parvin) complex serves as a link between integrins and components of growth factor receptor kinase and GTPase signaling pathways. Accordingly, PINCH-mediated signaling induces cell migration, spreading, and survival. Further research on the signaling cascades affected by PINCH is key to appreciating its biological significance in cell fate and systems maintenance, as the developmental functions of PINCH may extend to disease states and the cellular response to damage. PINCH is implicated in a diverse array of diseases including renal failure, cardiomyopathy, nervous system degeneration and demyelination, and tumorigenesis. This review presents evidence for PINCH's structural and functional importance in normal cellular processes and in pathogenesis. The current data for PINCH expression in nervous system disease is substantial, but due to the complex and ubiquitous nature of this protein, our understanding of its function in pathology remains unclear. In this review, an overview of studies identifying PINCH binding partners, their molecular interactions, and the potentially overlapping role(s) of PINCH in cancer and in nervous system diseases will be discussed. Many questions remain regarding PINCH's role in cells. What induces cell-specific PINCH expression? How does PINCH expression contribute to cell fate in the central nervous system? More broadly, is PINCH expression in disease a good thing? Clarifying the ambiguous functions of PINCH expression in the central nervous system and other systems is important to understand more clearly signaling events both in health and disease.
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