Activation of Src family members is not required for the platelet-derived growth factor β receptor to initiate mitogenesis
Activation of Src family members is not required for the platelet-derived growth factor β receptor to initiate mitogenesis
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DOI：
10.1128/mcb.18.4.2014
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发表时间：
1998-04-01
影响因子：
5.3
通讯作者：
Kazlauskas, A
中科院分区：
文献类型：
--
作者：
DeMali, KA;Kazlauskas, A
Src家族激酶的基础活性在整个细胞周期中都很容易检测到，并且在细胞受到生长因子（如血小板来源的生长因子）的急性刺激时，其活性会增加2至5倍。先前的报道已经证明，Src活性对于G(1)/S和G(2)/M转换是必需的。随着嵌合α - β PDGF受体（PDGFR）在成纤维细胞中表达，我们研究了PDGF介导的Src活性在G(0)/G(1)的重要性，在随后的细胞周期事件的转变中，一个突变的PDGFR嵌合体不能检测到与Src相关或激活Src，其介导受体相关信号分子酪氨酸磷酸化的能力受到损害，并启动了Erk的亚极大激活。与这些早期细胞周期事件相反，当Src活性在PDGF急性刺激后没有增加时，细胞进入S期和细胞增殖等后期反应正常进行。我们得出结论，SPS活性的初始hurst是有效酪氨酸磷酸化受体相关蛋白（如PLC γ， RasGAP， Shc和SHP-2）和Erk的最大激活所必需的，令人惊讶的是，这些事件不是pdgf依赖性细胞增殖所必需的。细胞周期后期的事件确实要求Src在G(0)/G(1)转变时被激活，这留下了G(1)/S转变等事件需要基础Src活性和/或在G(1)后期激活Src的可能性。
The basal activity of Src family kinases is readily detectable throughout the cell cycle and increases by two- to fivefold upon acute stimulation of cells with growth factors such as platelet-derived grow th factor, Previous reports have demonstrated a requirement for Src activity for the G(1)/S and G(2)/M transitions. With a chimeric alpha-beta PDGF receptor (PDGFR) expressed in fibroblasts, we have investigated the importance of the PDGF-mediated increase in Src activity at the G(0)/G(1), transition for subsequent cell cycle events, A mutant PDGFR chimera that was not able to detectably associate with or activate Src was compromised in its ability to mediate tyrosine phosphorylation of receptor-associated signaling molecules and initiated a submaximal activation of Erk. In contrast to these early cell cycle events, later responses such as entry of cells into S phase and cell proliferation proceeded normally when Src activity did not increase following acute stimulation with PDGF. We conclude that the initial hurst of SPS activity is required for efficient tyrosine phosphorylation of receptor-associated proteins such as PLC gamma, RasGAP, Shc, and SHP-2 and for maximal activation of Erk, Surprisingly, these events are not required for PDGF-dependent cell proliferation, Finally, later cell cycle events do meet require that Src be activated at the G(0)/G(1) transition acid leave open the possibility that events such as the G(1)/S transition require the basal Src activity and/or activation of Src at later times in G(1).