Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE-751 24, Uppsala, Sweden.
Cell Signal. 2010 Jun;22(6):955-60. doi: 10.1016/j.cellsig.2010.01.020. Epub 2010 Feb 6.
Extracellular regulated kinase (Erk) 5 is a member of the mitogen activated protein (MAP) kinase family that has been implicated in both cell proliferation and survival. In the present study, we found that stimulation with platelet-derived growth factor (PDGF)-BB leads to a transient activation of Erk5, which was shown to be dependent on recruitment of both Src kinases and the tyrosine phosphatase Shp2 to the activated PDGF receptor beta (PDGFRbeta). We could also demonstrate that Shp2 docking to the receptor is critical for Src kinase activation, suggesting that Shp2 may contribute to Erk5 activation through its involvement in Src kinase activation. Under control conditions, PDGF-BB promoted a sustained Akt phosphorylation. However, reduction of the expression of Erk5 by siRNA resulted in only a transient Akt phosphorylation, and an inability of PDGF-BB to suppress caspase 3 activation and inhibit apoptotic nuclear morphological changes such as condensed or fragmented chromatin under serum-free conditions.
细胞外调节激酶（Erk）5 是丝裂原激活蛋白（MAP）激酶家族的一员，它与细胞增殖和存活有关。在本研究中，我们发现血小板衍生生长因子（PDGF）-BB 的刺激导致 Erk5 的短暂激活，这依赖于Src 激酶和酪氨酸磷酸酶 Shp2 募集到激活的 PDGF 受体β（PDGFRβ）。我们还可以证明 Shp2 与受体的对接对于 Src 激酶的激活至关重要，这表明 Shp2 可能通过参与 Src 激酶的激活来促进 Erk5 的激活。在对照条件下，PDGF-BB 促进 Akt 的持续磷酸化。然而，通过 siRNA 降低 Erk5 的表达仅导致 Akt 的短暂磷酸化，并且 PDGF-BB 无法抑制无血清条件下 caspase 3 的激活和抑制凋亡核形态变化，如浓缩或碎片化染色质。
