Role of focal adhesion kinase in signaling by the extracellular matrix.
Role of focal adhesion kinase in signaling by the extracellular matrix.
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DOI：
10.1007/978-3-642-59766-4_3
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发表时间：
2000
影响因子：
--
通讯作者：
J. Zhao;J. Guan
中科院分区：
文献类型：
--
作者：
J. Zhao;J. Guan
细胞与细胞外基质（ECM）的相互作用在许多生物学过程中发挥重要作用，如胚胎发育和形态发生，伤口愈合和恶性转化。ECM的主要细胞表面受体是整联蛋白家族细胞粘附分子，其由非共价缔合的α和β亚基组成（Hynes 1992）。α和β亚基都是含有短胞质结构域的跨膜蛋白，其可以直接或间接地与细胞骨架蛋白如talin、黏着斑蛋白、α-辅肌动蛋白和细丝蛋白相互作用（Burridge等，1992; Hynes 1992）。除了作为ECM和细胞骨架之间的连接物外，整联蛋白已显示介导跨质膜的生化信号转导以调节各种细胞功能（Juliano和Haskill 1993; Clark和Brugge 1995; Schwartz等1995）。整合素介导的细胞粘附可以调节基因表达、细胞内pH和钙、磷脂代谢物、小GT酶、蛋白丝氨酸/苏氨酸激酶和蛋白酪氨酸磷酸化。由于整联蛋白具有短的无酶活性的胞质结构域，因此认为整联蛋白胞质结构域与胞质酪氨酸激酶、磷酸酶和衔接子分子的偶联在启动由整联蛋白介导的多种胞内信号传导途径中是关键的（Clark and Brugge 1995; Juliano and Haskill 1993; Schwartz等，1995）。粘着斑激酶（FAK）是一种细胞质蛋白酪氨酸激酶，其在整联蛋白介导的信号转导途径中起重要作用（Clark和Brugge 1995; Schwartz等1995; Parsons 1996）。FAK在整联蛋白介导的细胞粘附中被激活并酪氨酸磷酸化，并与整联蛋白和其他细胞骨架蛋白共定位于多种粘附细胞的病灶接触中（Schwartz et al. 1995）。已经描述了编码来自禽类（Schlauer等，1992）、鼠（Hanks等，1992）、人（Andre和Becker-Andre，1993; Whitney等，1993）和非洲爪蟾（Hens和DeSimone，1995）的FAK的cDNA。的比较
Cellular interactions with extracellular matrix (ECM) play important roles in many biological processes such as embryonic development and morphogenesis, wound healing, and malignant transformation. The major cell surface receptors for ECM are the integrin family cell adhesion molecules which are composed of noncovalently associated a and p subunits (Hynes 1992). Both a and p subunits are transmembrane proteins containing short cytoplasmic domains that can interact directly or indirectly with cytoskeletal proteins such as talin, vinculin, a-actinin, and filamin (Burridge et al. 1992; Hynes 1992). Besides serving as a linker between ECM and cytoskeleton, integrins have been shown to mediate biochemical signal transduction across the plasma membrane to regulate various cellular functions (Juliano and Haskill 1993; Clark and Brugge 1995; Schwartz et al. 1995). Integrin-mediated cell adhesion can regulate gene expression, intracellular pH and calcium, phospholipid metabolites, small GTPase, protein serine/threonine kinases, and protein tyrosine phosphorylation. Since integrins have short cytoplasmic domains with no enzymatic activities, it is believed that coupling of the integrin cytoplasmic domains with cytoplasmic tyrosine kinases, phosphatases, and adaptor molecules are critical in initiating multiple intracellular signaling pathways mediated by integrins (Clark and Brugge 1995; Juliano and Haskill 1993; Schwartz et al. 1995).Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase which has been implicated in playing an important role in integrin-mediated signal transduction pathways (Clark and Brugge 1995; Schwartz et al. 1995; Parsons 1996). FAK becomes activated and tyrosine phosphorylated in integrinmediated cell adhesion and is colocalized with integrins and other cytoskeletal proteins in focal contacts in a variety of adherent cells (Schwartz et al. 1995). cDNAs encoding FAK from avian (Schaller et al. 1992), murine (Hanks et al. 1992), human (Andre and Becker-Andre 1993; Whitney et al. 1993), and Xenopus (Hens and DeSimone 1995) have been described. The comparison of