A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob
A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob
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DOI：
10.1046/j.1365-2443.2001.00406.x
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发表时间：
2001-02-01
期刊：
影响因子：
2.1
通讯作者：
Yamamoto, T
中科院分区：
文献类型：
--
作者：
Suzuki, T;Matsuda, S;Yamamoto, T
背景：tob是具有抗增殖功能的基因家族的成员。 Tob 在 NIH3T3 细胞中过度表达会导致细胞抑制。增殖。激活的 ErbB2 激酶的存在阻碍了生长抑制。 Tob 抑制细胞生长和 ErbB2 消除 Tob 功能的分子机制仍有待阐明。结果：我们发现，Tob 在丝氨酸和苏氨酸上被磷酸化，但在酪氨酸上不被磷酸化，该激酶在各种细胞（包括 ErbB2 过表达细胞）的裂解物中与 Tob 相关联。我们还表明 95 kDa 激酶在体外与 Tob 相关。该激酶的自磷酸化活性与 Tob 磷酸化活性共色谱，表明 95 kDa 激酶磷酸化 Tob。在已知的分子量约为 95 kDa 的激酶中，p90rsk1 在体外和体内与 Tob 结合，并且至少在体外磷酸化 Tob。因此，p90rsk1很可能代表95 kDa激酶，并通过磷酸化参与Tob功能的调节。结论：p90rsk1与Tob结合并磷酸化Tob。由于 p90rsk1 在受体酪氨酸激酶下游被激活，因此我们认为 Tob 功能至少部分受到生长因子刺激的酪氨酸激酶通过 p90rsk1 磷酸化的控制。
Background: tob is a member of a gene family with antiproliferative function. Over-expression of Tob in NIH3T3 cells results in the suppression of cell. proliferation. The growth suppression is hampered by the presence of activated ErbB2 kinase. The molecular mechanisms by which Tob suppresses cell growth and by which ErbB2 abrogates Tob function remain to be elucidated.Results: We show that Tob is phosphorylated on serines and threonines, but not tyrosines, by a kinase(s) that associates with Tob in the lysates of various cells, including ErbB2-over-expressed cells. We also show that a 95 kDa kinase associates with Tob in vitro. The autophosphorylation activity of this kinase co-chromatographes with Tob-phosphorylating activity, suggesting that the 95 kDa kinase phosphorylates Tob. Among the known kinases with molecular mass around 95 kDa, p90rsk1 associates with Tob in vitro and in vivo, and phosphorylates Tob at least in vitro. Therefore, it is likely that p90rsk1 represents the 95 kDa kinase and is involved in the regulation of Tob function through phosphorylation.Conclusion: p90rsk1 associates with and phosphorylates Tob. Because p90rsk1 is activated downstream of receptor tyrosine kinases, we propose that Tob function is at least in part under the control of growth factor-stimulated tyrosine kinases through its phosphorylation by p90rsk1.