van der Heyden M A, Van Bergen en Henegouwen P M, de Ruiter N, Verdaasdonk M A, van den Tweel J G, Rijksen G, Boonstra J, Joling P
Department of Molecular Cell Biology, Utrecht University, The Netherlands.
Exp Cell Res. 1997 Aug 1;234(2):521-6. doi: 10.1006/excr.1997.3661.
NIH-3T3 fibroblasts expressing epidermal growth factor receptors (EGFRs) lacking the actin binding domain (ABD) were analyzed for their EGF-induced capacity to invade a bone marrow stromal cell (BMSC) monolayer. The fibroblasts display a reduction in the percentage of cytoskeleton-associated EGFRs. Furthermore, EGF-induced tyrosine kinase activity is unaffected by the mutation. Cells expressing the mutant EGFRs hardly invade a BMSC monolayer upon EGF stimulation in contrast to cells expressing wild-type EGFRs. Using the same cells no difference was observed in PDGF-induced invasion, which ligand was as potent in both cell types as EGF was in wild-type cells. Inhibition of both the phosphatidyl inositol-3-kinase (PI-3-K) and lipoxygenase pathways in wild-type cells mimicked the effect of the ABD deletion. Our results point to an important role for the ABD of the EGFR in EGF-induced tissue invasion.
对表达缺乏肌动蛋白结合结构域（ABD）的表皮生长因子受体（EGFR）的NIH-3T3成纤维细胞进行分析，以研究其在表皮生长因子（EGF）诱导下侵袭骨髓基质细胞（BMSC）单层的能力。成纤维细胞中与细胞骨架相关的EGFR百分比降低。此外，EGF诱导的酪氨酸激酶活性不受该突变影响。与表达野生型EGFR的细胞相比，表达突变型EGFR的细胞在EGF刺激下几乎不侵袭BMSC单层。使用相同的细胞，在血小板衍生生长因子（PDGF）诱导的侵袭中未观察到差异，该配体在两种细胞类型中的效力与EGF在野生型细胞中的效力相同。野生型细胞中磷脂酰肌醇-3-激酶（PI-3-K）和脂氧合酶途径的抑制模拟了ABD缺失的效果。我们的结果表明EGFR的ABD在EGF诱导的组织侵袭中起重要作用。
