Schaller M D, Otey C A, Hildebrand J D, Parsons J T
Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908, USA.
J Cell Biol. 1995 Sep;130(5):1181-7. doi: 10.1083/jcb.130.5.1181.
The integrins have recently been implicated in signal transduction. A likely mediator of integrin signaling is focal adhesion kinase (pp125FAK or FAK), a structurally distinct protein tyrosine kinase that becomes enzymatically activated upon engagement of integrins with their ligands. A second candidate signaling molecule is paxillin, a focal adhesion associated, cytoskeletal protein that coordinately becomes phosphorylated on tyrosine upon activation of pp125FAK. Paxillin physically complexes with two protein tyrosine kinases, pp60src and Csk (COOH-terminal src kinase), and the oncoprotein p47gag-crk, each of which could function as part of a paxillin signaling complex. Using an in vitro assay we have established that the cytoplasmic domain of the beta 1 integrin can bind to paxillin and pp125FAK from chicken embryo cell lysates. The NH2-terminal, noncatalytic domain of pp125FAK can bind directly to the cytoplasmic tail of beta 1 and recognizes integrin sequences distinct from those involved in binding to alpha-actinin. Paxillin binding is independent of pp125FAK binding despite the fact that both bind to the same region of beta 1. These results demonstrate that the cytoplasmic domain of the beta subunits of integrins contain binding sites for both signaling molecules and structural proteins suggesting that integrins can coordinate the generation of cytoplasmic signals in addition to their role in anchoring components of the cytoskeleton.
整合素最近被认为与信号转导有关。整合素信号转导的一个可能介质是粘着斑激酶(pp125FAK或FAK),它是一种结构上不同的蛋白酪氨酸激酶,在整合素与其配体结合时被酶激活。第二个候选信号分子是桩蛋白,一种与粘着斑相关的细胞骨架蛋白,在pp125FAK激活时酪氨酸会协同磷酸化。桩蛋白与两种蛋白酪氨酸激酶pp60src和Csk(COOH末端src激酶)以及癌蛋白p47gag-crk形成物理复合物,它们每一个都可能作为桩蛋白信号复合物的一部分发挥作用。通过体外试验,我们已经证实β1整合素的胞质结构域可以与鸡胚细胞裂解物中的桩蛋白和pp125FAK结合。pp125FAK的NH2末端非催化结构域可以直接与β1的胞质尾巴结合,并识别与结合α-辅肌动蛋白不同的整合素序列。尽管桩蛋白和pp125FAK都与β1的同一区域结合,但桩蛋白的结合与pp125FAK的结合无关。这些结果表明,整合素β亚基的胞质结构域包含信号分子和结构蛋白的结合位点,这表明整合素除了在锚定细胞骨架成分方面发挥作用外,还可以协调胞质信号的产生。