化学遗传学确定c-Src为小鼠胚胎干细胞中原始外胚层形成的激活因子。
Chemical genetics identifies c-Src as an activator of primitive ectoderm formation in murine embryonic stem cells.
作者信息
Meyn Malcolm A, Smithgall Thomas E
机构信息
University of Pittsburgh School of Medicine, Department of Microbiology and Molecular Genetics, Pittsburgh, PA 15213-2536, USA.
出版信息
Sci Signal. 2009 Oct 13;2(92):ra64. doi: 10.1126/scisignal.2000311.
Abstract
Multiple Src family kinases (SFKs) are present in murine embryonic stem (mES) cells. Whereas complete inhibition of SFK activity blocks mES cell differentiation, sole inhibition of the SFK member c-Yes induces differentiation. Thus, individual SFKs may have opposing roles in the regulation of mES cell fate. To test this possibility, we generated SFK mutants with engineered resistance to a nonselective SFK inhibitor. The presence of an inhibitor-resistant c-Src mutant, but not analogous mutants of Hck, Lck, c-Yes, or Fyn, reversed the differentiation block associated with inhibitor treatment, resulting in the formation of cells with properties of primitive ectoderm. These results show that distinct SFK signaling pathways regulate mES cell fate and demonstrate that the formation of primitive ectoderm is regulated by the activity of c-Src.
摘要
多种Src家族激酶（SFK）存在于小鼠胚胎干细胞（mES细胞）中。虽然完全抑制SFK活性会阻止mES细胞分化，但单独抑制SFK成员c-Yes会诱导分化。因此，单个SFK在mES细胞命运调控中可能具有相反的作用。为了验证这种可能性，我们构建了对非选择性SFK抑制剂具有工程抗性的SFK突变体。存在抑制剂抗性的c-Src突变体，但Hck、Lck、c-Yes或Fyn的类似突变体不存在时，可逆转与抑制剂处理相关的分化阻滞，导致形成具有原始外胚层特性的细胞。这些结果表明，不同的SFK信号通路调节mES细胞命运，并证明原始外胚层的形成受c-Src活性的调控。
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