Platelet-derived growth factor-stimulated migration of murine fibroblasts is associated with epidermal growth factor receptor expression and tyrosine phosphorylation
Platelet-derived growth factor-stimulated migration of murine fibroblasts is associated with epidermal growth factor receptor expression and tyrosine phosphorylation
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DOI：
10.1074/jbc.275.4.2951
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发表时间：
2000-01-28
影响因子：
4.8
通讯作者：
Bertics, PJ
中科院分区：
文献类型：
--
作者：
Li, J;Kim, YN;Bertics, PJ
先前的研究表明，表皮生长因子（EGF）与各种细胞外基质成分协同作用，促进表达野生型EGF受体的B82 L成纤维细胞的迁移，并且功能性EGF受体对于B82 L成纤维细胞转化为迁移细胞类型至关重要（1）。在本研究中，我们研究了血小板衍生生长因子（PDGF）对B82 L成纤维细胞的运动的影响，使用微趋化室。我们发现，PDGF可以增强表达野生型EGF受体的B82 L成纤维细胞（B82 L-克隆B3）的纤连蛋白诱导的迁移。然而，缺乏EGF受体（B82 L-亲本）或表达激酶失活的EGF受体（BS 2L-K721 M）或C末端截短的EGF受体（B82 L-c ′ 973）的B82 L细胞几乎不显示PDGF刺激的迁移。此外，这三种细胞系都没有表现出单独迁移至纤连蛋白的能力。这些观察结果表明，类似于细胞向纤连蛋白的迁移，PDGF诱导的B82 L成纤维细胞的细胞迁移通过完整的EGF受体激酶的表达而增强。在不表达完整EGF受体的E82 L细胞中，PDGF刺激的运动性的丧失似乎不是由PDGF受体的总体功能障碍引起的，因为在这些细胞中容易检测到配体刺激的PDGP-β受体的酪氨酸磷酸化和促分裂原活化蛋白激酶的活化。此外，EGF和PDGF受体系统之间的相互作用得到以下观察结果的支持，即EGF受体在加入PDGF后表现出磷酸酪氨酸含量以时间依赖性方式增加。总之，这些研究表明，EGF受体的表达对于PDGF刺激的鼠B82 L成纤维细胞的迁移是至关重要的，并表明EGF受体在导致PDGF刺激的细胞运动性的信号传导事件中在PDGF受体活化的下游发挥作用。
Previous studies have shown that epidermal growth factor (EGF) synergizes with various extracellular matrix components in promoting the migration of B82L fibroblasts expressing wild-type EGF receptors and that functional EGF receptors are critical for the conversion of B82L fibroblasts to a migratory cell type (1). In the present study, we examined the effects of platelet-derived growth factor (PDGF) on the motility of B82L fibroblasts using a microchemotaxis chamber. We found that PDGF can enhance fibronectin-induced migration of B82L fibroblasts expressing wild-type EGF receptors (B82L-clone B3), However, B82L cells that lack the EGF receptor (B82L-parental) or that express an EGF receptor that is kinase-inactive (BS2L-K721M) or C-terminally truncated (B82L-c'973) exhibit little PDGF-stimulated migration. In addition, none of these three cell lines exhibit the capacity to migrate to fibronectin alone. These observations indicate that, similar to cell migration toward fibronectin, PDGF-induced cell migration of B82L fibroblasts is augmented by the expression of an intact EGF receptor kinase. The loss of PDGF-stimulated motility in E82L cells that do not express an intact EGF receptor does not appear to result from a gross dysfunction of PDGF receptors, because ligand-stimulated tyrosine phosphorylation of the PDGP-beta receptor and the activation of mitogen-activated protein kinases are readily detectable in these cells. Moreover, an interaction between EGF and PDGF receptor systems is supported by the observation that the EGF receptor exhibits an increase in phosphotyrosine content in a time-dependent fashion upon the addition of PDGF. Altogether, these studies demonstrate that the expression of EGF receptor is critical for PDGF-stimulated migration of murine B82L fibroblasts and suggest a role for the EGF receptor do downstream of PDGF receptor activation in the signaling events that lead to PDGF-stimulated cell motility.