Laboratory of Human Anatomy and Cell Biology, Faculty of Health Sciences, Tsukuba University of Technology, 305-8521 Tsukuba, Japan.
Front Biosci (Landmark Ed). 2024 Nov 20;29(11):392. doi: 10.31083/j.fbl2911392.
Cell-to-substrate adhesion sites, also known as focal adhesion sites (FAs), are complexes of different proteins on the cell surface. FAs play important roles in communication between cells and the extracellular matrix (ECM), leading to signal transduction involving different proteins that ultimately produce the cell response. This cell response involves cell adhesion, migration, motility, cell survival, and cell proliferation. The most important component of FAs are integrins. Integrins are transmembrane proteins that receive signals from the ECM and communicate them to the cytoplasm, thus activating several downstream proteins in a signaling cascade. Cellular Proto-oncogene tyrosine-protein kinase Src (c-Src) and focal adhesion kinase (FAK) are non-receptor tyrosine kinases that functionally interact to promote crucial roles in FAs. c-Src is a tyrosine kinase, activated by autophosphorylation and, in turn, activates another important protein, FAK. Activated FAK directly interacts with the cytoplasmic domain of integrin and activates other FA proteins by attaching to them. These proteins activated by FAK then activate other downstream pathways such as mitogen-activated protein kinase (MAPK) and Akt pathways involved in cell proliferation, migration, and cell survival. Src can induce detachment of FAK from the integrin to increase the focal adhesion turnover. As a result, the Src-FAK complex in FAs is critical for cell adhesion and survival mechanisms. Overexpression of FA proteins has been linked to a variety of pathological disorders, including cancers, growth retardation, and bone deformities. FAK and Src are overexpressed in various cancers. This review, which focuses on the roles of two important signaling proteins, c-Src and FAK, attempts to provide a thorough and up-to-date examination of the signal transduction mechanisms mediated by focal adhesions. The author also described that FAK and Src may serve as potential targets for future therapies against diseases associated with their overexpression, such as certain types of cancer.
细胞-基质黏附位点，也称为黏着斑（FA），是细胞表面不同蛋白质的复合物。FA 在细胞与细胞外基质（ECM）之间的通讯中发挥重要作用，导致涉及不同蛋白质的信号转导，最终产生细胞反应。这种细胞反应涉及细胞黏附、迁移、运动、细胞存活和细胞增殖。FA 的最重要组成部分是整合素。整合素是一种跨膜蛋白，它接收来自 ECM 的信号并将其传递到细胞质中，从而在信号级联中激活几个下游蛋白。细胞原癌基因酪氨酸蛋白激酶 Src（c-Src）和黏着斑激酶（FAK）是细胞内非受体酪氨酸激酶，它们在功能上相互作用，在 FA 中发挥重要作用。c-Src 是一种酪氨酸激酶，通过自身磷酸化激活，进而激活另一种重要蛋白 FAK。激活的 FAK 直接与整合素的细胞质结构域相互作用，并通过与它们结合来激活其他 FA 蛋白。FAK 激活的这些蛋白随后激活其他下游途径，如参与细胞增殖、迁移和细胞存活的丝裂原活化蛋白激酶（MAPK）和 Akt 途径。Src 可以诱导 FAK 从整合素上脱离，从而增加焦点黏附的周转率。因此，FA 中的 Src-FAK 复合物对于细胞黏附和存活机制至关重要。FA 蛋白的过表达与多种病理疾病有关，包括癌症、生长迟缓症和骨骼畸形。在各种癌症中，FAK 和 Src 过表达。这篇综述重点关注两个重要信号蛋白 c-Src 和 FAK 的作用，试图对焦点黏附介导的信号转导机制进行全面和最新的检查。作者还描述了 FAK 和 Src 可能作为未来针对与它们过表达相关疾病（如某些类型的癌症）的治疗的潜在靶点。
