Involvement of phosphatases in the anchorage-dependent regulation of ERK2 activation
Involvement of phosphatases in the anchorage-dependent regulation of ERK2 activation
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DOI：
10.1016/j.yexcr.2007.03.001
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发表时间：
2007-05-15
影响因子：
3.7
通讯作者：
Kioka, Noriyuki
中科院分区：
文献类型：
--
作者：
Mitsushima, Masaru;Ueda, Kazumitsu;Kioka, Noriyuki
细胞外信号调节激酶（ERK）的激活已知受细胞粘附调节，即“锚定依赖性”。大多数关于锚定依赖性调节的研究都集中在上游激活成分上。我们以前报道过黏着斑蛋白vinexin β可以诱导ERK 2的锚定非依赖性激活。我们在这里表明，vinexin β诱导的ERK 2的锚定非依赖性激活涉及防止ERK 2的去磷酸化，但不促进MEK 1或Raf 1活性。此外，vinexin β的敲低导致A549细胞中ERK 2的更快去磷酸化。此外，共表达的MKP 3/rVH 6，ERK 2特异性磷酸酶，抑制锚定非依赖性激活的ERK 2诱导vinexin β。这些结果表明，vinexin β可以阻止由细胞脱离刺激的ERK 2的去磷酸化，导致ERK 2的锚定非依赖性激活。此外，我们发现，磷酸酶活性针对活化的ERK 2是更高的悬浮细胞比贴壁细胞。此外，在NIH 3 T3细胞中，原钒酸盐有效地诱导ERK 2的锚定非依赖性激活，而不显著激活MEK 1。这些观察结果表明，ERK 1/2激活的锚定依赖性不仅受到上游激酶Raf 1和MEK的调节，而且还受到针对ERK 1/2的磷酸酶的调节，并且vinexin β可以通过阻止ERK 1/2的失活来诱导ERK的锚定非依赖性激活。(c)2007年爱思唯尔公司All rights reserved.
Activation of extracellular signal-regulated kinase (ERK) is known to be regulated by cell adhesion, namely "anchorage dependence". Most studies on the anchorage-dependent regulation have focused on the upstream activating components. We previously reported that the focal adhesion protein vinexin beta can induce the anchorage-independent activation of ERK2. We show here that vinexin beta-induced anchorage-independent activation of ERK2 involves prevention of the dephosphorylation of ERK2, but not the promotion of MEK1 or Raf1 activity. Furthermore, knockdown of vinexin beta resulted in a faster dephosphorylation of ERK2 in A549 cells. Moreover, the coexpression of MKP3/rVH6, an ERK2 specific phosphatase, suppressed the anchorage-independent activation of ERK2 induced by vinexin beta. These results suggest that vinexin beta can prevent the dephosphorylation of ERK2 stimulated by cell detachment, leading to the anchorage-independent activation of ERK2. Furthermore, we found that phosphatase activity directed against activated ERK2 was higher in suspended cells than in adherent cells. in addition, orthovanadate efficiently induces anchorage-independent activation of ERK2 without marked activation of MEK1 in NIH3T3 cells. These observations suggest that the anchorage dependence of ERK1/2 activation is regulated not only by upstream kinases, Raf1 and MEK, but also by phosphatases acting against ERK1/2 and that vinexin beta can induce anchorage-independent activation of ERK by preventing the inactivation of ERK1/2. (c) 2007 Elsevier Inc. All rights reserved.