将PC12细胞暴露于表皮生长因子（EGF）和神经生长因子（NGF）后，真核起始因子4E结合蛋白PHAS-I的磷酸化。
Phosphorylation of the eIF4E-binding protein PHAS-I after exposure of PC12 cells to EGF and NGF.
作者信息
Kleijn M, Korthout M M, Voorma H O, Thomas A A
机构信息
Utrecht University, Department of Molecular Cell Biology, The Netherlands.
出版信息
FEBS Lett. 1996 Nov 4;396(2-3):165-71. doi: 10.1016/0014-5793(96)01097-6.
PHAS-I or the eIF4E-binding protein 1 regulates the cap-binding activity of eIF4E by sequestering eIF4E. Binding of elF4E to PHAS-I is regulated by phosphorylation of PHAS-I. PC12 cells were used to study the signal transduction pathway leading to phosphorylation of PHAS-I. Both EGF and NGF induced phosphorylation of PHAS-I. Wortmannin, a PI-3 kinase inhibitor, staurosporine, a PKC inhibitor, and rapamycin, a FRAP inhibitor all blocked the phosphorylation of PHAS-I. Of the three inhibitors, only wortmannin was able to inhibit MAPK phosphorylation. This excludes a role for MAPK in NGF- and EGF-induced PHAS-I phosphorylation in PC12 cells. Apparently, PHAS-I was phosphorylated in a PI-3 kinase-, PKC-, and FRAP-dependent manner after EGF or NGF stimulation. Only PI-3 kinase and FRAP are involved in the regulation of the basal level of PHAS-I phosphorylation.
PHAS-I 即真核起始因子4E结合蛋白1，通过隔离真核起始因子4E（eIF4E）来调节其帽结合活性。eIF4E与PHAS-I的结合受PHAS-I磷酸化的调控。利用PC12细胞研究导致PHAS-I磷酸化的信号转导途径。表皮生长因子（EGF）和神经生长因子（NGF）均可诱导PHAS-I磷酸化。磷脂酰肌醇-3激酶（PI-3激酶）抑制剂渥曼青霉素、蛋白激酶C（PKC）抑制剂星形孢菌素以及FK506结合蛋白12-雷帕霉素相关蛋白（FRAP）抑制剂雷帕霉素均能阻断PHAS-I的磷酸化。在这三种抑制剂中，只有渥曼青霉素能够抑制丝裂原活化蛋白激酶（MAPK）的磷酸化。这排除了MAPK在PC12细胞中NGF和EGF诱导的PHAS-I磷酸化过程中的作用。显然，在EGF或NGF刺激后，PHAS-I以依赖PI-3激酶、PKC和FRAP的方式发生磷酸化。只有PI-3激酶和FRAP参与PHAS-I基础磷酸化水平的调节。
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