Hu Lianxin, Huang Hongling, Li Jinhui, Yin Meng-Xin, Lu Yi, Wu Wenqing, Zeng Rong, Jiang Jin, Zhao Yun, Zhang Lei
From the State Key Laboratory of Cell Biology and.
Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yue-Yang Road, Shanghai 200031, China and.
J Biol Chem. 2014 Nov 28;289(48):33598-607. doi: 10.1074/jbc.M114.580456. Epub 2014 Oct 15.
Drosophila Hippo signaling regulates Wts activity to phosphorylate and inhibit Yki in order to control tissue growth. CK2 is widely expressed and involved in a variety of signaling pathways. In this study we report that Drosophila CK2 promotes Wts activity to phosphorylate and inhibit Yki activity, which is independent of Hpo-induced Wts promotion. In vivo, CK2 overexpression suppresses hpo mutant-induced expanded (Ex) up-regulation and overgrowth phenotype, whereas it cannot affect wts mutant. Consistent with this, knockdown of CK2 up-regulates Hpo pathway target expression. We also found that Drosophila CK2 is essential for tissue growth as a cell death inhibitor as knockdown of CK2 in the developing disc induces severe growth defects as well as caspase3 signals. Taken together, our results uncover a dual role of CK2; although its major role is promoting cell survive, it may potentially be a growth inhibitor as well.
果蝇的Hippo信号通路调节Wts活性,使其磷酸化并抑制Yki,从而控制组织生长。CK2广泛表达并参与多种信号通路。在本研究中,我们报告果蝇CK2促进Wts活性,使其磷酸化并抑制Yki活性,这一作用独立于Hpo诱导的Wts激活。在体内,CK2过表达抑制hpo突变体诱导的扩展(Ex)上调和过度生长表型,但不影响wts突变体。与此一致,敲低CK2会上调Hpo通路靶标的表达。我们还发现,果蝇CK2作为细胞死亡抑制剂对组织生长至关重要,因为在发育中的翅芽中敲低CK2会导致严重的生长缺陷以及caspase3信号。综上所述,我们的结果揭示了CK2的双重作用;尽管其主要作用是促进细胞存活,但它也可能是一种生长抑制剂。