Drosophila C-terminal Src kinase negatively regulates organ growth and cell proliferation through inhibition of the Src, Jun N-terminal kinase, and STAT pathways
Drosophila C-terminal Src kinase negatively regulates organ growth and cell proliferation through inhibition of the Src, Jun N-terminal kinase, and STAT pathways
复制标题
DOI：
10.1128/mcb.24.15.6676-6689.2004
复制
发表时间：
2004-08-01
影响因子：
5.3
通讯作者：
Cagan, RL
中科院分区：
文献类型：
--
作者：
Read, RD;Bach, EA;Cagan, RL
Src家族激酶调节多种细胞过程，包括增殖和肿瘤发生。C-末端Src激酶（Csk）编码Sire家族激酶的关键负调节因子。我们证明，果蝇Csk的直系同源物，dCsk，作为一种肿瘤抑制因子的功能：dCsk突变体显示器官过度生长和过度细胞增殖。遗传分析表明，dCsk（-/-）过度生长表型的Src，Jun激酶，STAT信号转导通路的激活的结果。特别是，阻断STAT功能的dCsk突变体严重减少Sirc依赖的过度生长和激活的突变组织的凋亡。我们的数据提供了Src活性需要JNK和STAT功能的体内证据。
Src family kinases regulate multiple cellular processes including proliferation and oncogenesis. C-terminal Src kinase (Csk) encodes a critical negative regulator of Sire family kinases. We demonstrate that the Drosophila melanogaster Csk ortholog, dCsk, functions as a tumor suppressor: dCsk mutants display organ overgrowth and excess cellular proliferation. Genetic analysis indicates that the dCsk(-/-) overgrowth phenotype results from activation of Src, Jun kinase, and STAT signal transduction pathways. In particular, blockade of STAT function in dCsk mutants severely reduced Sirc-dependent overgrowth and activated apoptosis of mutant tissue. Our data provide in vivo evidence that Src activity requires JNK and STAT function.