De Nichilo M O, Katz B Z, O'Connell B, Yamada K M
Craniofacial Developmental Biology and Regeneration Branch, NIDCR, NIH, Bethesda, Maryland 20892-4370, USA.
J Cell Physiol. 1999 Feb;178(2):164-72. doi: 10.1002/(SICI)1097-4652(199902)178:2<164::AID-JCP5>3.0.CO;2-R.
The protein tyrosine kinase pp125FAK (focal adhesion kinase, or FAK) is expressed by a variety of cell types and has been implicated in integrin-mediated signaling events. We explored the potential functions of FAK by expressing it de novo in a cell type lacking FAK. We showed previously that cultured human macrophages lack FAK yet still have well-formed focal contacts. Adenovirus-mediated expression of FAK results in the appearance of FAK protein, which localizes to focal contacts and becomes tyrosine-phosphorylated without perturbing overall cell morphology or focal contacts. FAK associates with CSK 48 h after infection and recruits it to focal contacts. Tyrosine phosphorylation of p130cas but not of paxillin is stimulated after FAK expression. The phosphorylation of p130cas is lost at 48 h in parallel with CSK accumulation in focal contacts. The ERK2 form of MAP kinase is similarly activated at 12-24 h, but it also returns to low levels at 48 h. These findings demonstrate that FAK can be reconstituted to focal contacts in cells that lack it without affecting cell morphology or focal contact structure. FAK can regulate the distribution and activities of elements of the MAP kinase signaling pathway.
蛋白酪氨酸激酶pp125FAK（粘着斑激酶，或FAK）在多种细胞类型中表达，并参与整合素介导的信号转导事件。我们通过在缺乏FAK的细胞类型中从头表达FAK来探索其潜在功能。我们之前表明，培养的人巨噬细胞缺乏FAK，但仍有形成良好的粘着斑。腺病毒介导的FAK表达导致FAK蛋白出现，其定位于粘着斑并发生酪氨酸磷酸化，而不会干扰整体细胞形态或粘着斑。感染后48小时，FAK与CSK结合并将其招募到粘着斑。FAK表达后刺激了p130cas而非桩蛋白的酪氨酸磷酸化。p130cas的磷酸化在48小时时消失，同时CSK在粘着斑中积累。丝裂原活化蛋白激酶的ERK2形式在12 - 24小时时同样被激活，但在48小时时也恢复到低水平。这些发现表明，FAK可以在缺乏它的细胞中重新构建到粘着斑中，而不影响细胞形态或粘着斑结构。FAK可以调节丝裂原活化蛋白激酶信号通路元件的分布和活性。
