A Role for C. elegans Eph RTK Signaling in PTEN Regulation
A Role for C. elegans Eph RTK Signaling in PTEN Regulation
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DOI：
10.1016/j.devcel.2009.08.009
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发表时间：
2009-10-20
影响因子：
11.8
通讯作者：
Chin-Sang, Ian
中科院分区：
文献类型：
--
作者：
Brisbin, Sarah;Liu, Jun;Chin-Sang, Ian
PTEN是人类癌症中最常见的肿瘤抑制因子之一，并且已知其抑制胰岛素信号传导。Eph受体酪氨酸激酶（RTK）也与癌症的形成和发展有关，它们具有多种功能，包括神经和血管系统发育。我们在C.在线虫中，VAB-1 Eph激酶结构域与PTEN（PTEN-18）物理相互作用并使其磷酸化，从而降低其蛋白水平和功能。vab-1突变体显示出增加的寿命和对dauer条件的敏感性，这与增加的β-18/PTEN活性和减少的胰岛素样信号传导一致。此外，daf-18突变抑制vab-1卵母细胞成熟表型独立于PI 3 K信号传导。我们还提出证据表明，β-18具有蛋白磷酸酶活性，拮抗VAB-1的行动。人类癌症的可能影响进行了讨论，基于PTEN和Eph RTK之间的相互抑制作用可能是保守的想法。
PTEN is one of the most commonly lost tumor suppressors in human cancer and is known to inhibit insulin signaling. Eph receptor tyrosine kinases (RTKs) have also been implicated in cancer formation and progression, and they have diverse functions, including nervous and vascular system development. We show that in C. elegans, the VAB-1 Eph kinase domain physically interacts with and phosphorylates PTEN (DAF-18), diminishing its protein levels and function. vab-1 mutants show increased longevity and sensitivity to dauer conditions, consistent with increased DAF-18/PTEN activity and decreased insulin-like signaling. Moreover, daf-18 mutations suppress vab-1 oocyte maturation phenotypes independent of PI3K signaling. We also present evidence that DAF-18 has protein phosphatase activity to antagonize VAB-1 action. Possible implications for human cancers are discussed, based on the idea that mutually inhibitory interactions between PTEN and Eph RTKs may be conserved.