Modulation of the epidermal growth factor receptor by platelet-derived growth factor and choleragen: effects on mitogenesis.
Modulation of the epidermal growth factor receptor by platelet-derived growth factor and choleragen: effects on mitogenesis.
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血小板源性生长因子和胆原对表皮生长因子受体的调节：对有丝分裂的影响。
DOI：
10.1073/pnas.79.18.5567
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发表时间：
1982
影响因子：
11.1
通讯作者：
O'Keefe,EJ
中科院分区：
文献类型：
--
作者：
Wharton,W;Leof,E;Pledger,WJ;O'Keefe,EJ
向 BALB/c-3T3 细胞的静态密度停滞培养物中添加补充有部分纯化的血小板衍生生长因子 (PDGF) 的新鲜培养基可减少放射性标记表皮生长因子 (EGF) 的后续结合。添加PDGF后1小时可以观察到EGF结合的减少。这种效果在 2-3 小时内达到最大，并且结合作用在至少 6 小时内保持减弱。这些效应可以通过 EGF 受体数量减少而受体亲和力没有变化来解释。 PDGF 的作用是浓度依赖性的，但即使在非常高的 PDGF 浓度下，EGF 结合的减少也不会超过 50%。通过使 BALB/c-3T3 细胞具有活性的其他处理，例如添加成纤维细胞生长因子或先前暴露于巨噬细胞样细胞系 P388D1 的培养基，也会产生类似的 EGF 结合减少。霍乱毒素（choleragen）单独对 EGF 结合没有影响，但却显着增强了 PDGF 下调 EGF 受体的能力。添加PDGF和霍原2至3小时后，与对照值相比，EGF结合减少80-90%。 PDGF 和胆原共同降低 EGF 结合的能力被放线菌酮显着抑制。 [3H]胸苷标记细胞的放射自显影显示，choleragen 增强了 PDGF 的作用；胆原处理后，需要较低浓度的 PDGF 使细胞具有活性。此外，用 PDGF 和霍乱原处理的细胞不再需要 EGF 来穿越 G1 期并在确定的培养基中启动 DNA 合成。胆原和PDGF产生的受体数量的减少，可能是由于EGF受体的内化，可能模仿EGF的作用，从而消除DNA合成所需的EGF。
The addition of fresh medium supplemented with partially purified platelet-derived growth factor (PDGF) to quiescent density-arrested cultures of BALB/c-3T3 cells decreases the subsequent binding of radiolabeled epidermal growth factor (EGF). The decrease in EGF binding can be observed 1 hr after the addition of PDGF. This effect is maximal in 2-3 hr, and binding remains diminished for at least 6 hr. These effects can be accounted for by a decrease in the number of EGF receptors with no change in receptor affinity. The action of PDGF is concentration dependent, but even at very high concentrations of PDGF the reduction in EGF binding is never more than 50%. Similar decreases in EGF binding are produced by other treatments that render BALB/c-3T3 cells competent, such as the addition of fibroblast growth factor or medium previously exposed to the macrophage-like cell line P388D1. Cholera toxin (choleragen), which alone had no effect on EGF binding, dramatically potentiated the ability of PDGF to down regulate EGF receptors. Two to three hours after the addition of PDGF and choleragen, EGF binding was reduced by 80-90% compared with control values. The ability of PDGF and choleragen together to decrease EGF binding was substantially inhibited by cycloheximide. Autoradiography of [3H]thymidine-labeled cells shows that choleragen potentiates the action of PDGF; lower concentrations of PDGF are required to make cells competent after choleragen treatment. Furthermore, cells treated with PDGF and choleragen no longer require EGF for traverse of G1phase and initiation of DNA synthesis in defined medium. The reduction in receptor number produced by choleragen and PDGF, which may be due to internalization of the EGF receptor, may mimic the action of EGF and thereby remove the EGF requirement for DNA synthesis.