Fu X Y, Zhang J J
Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029.
Cell. 1993 Sep 24;74(6):1135-45. doi: 10.1016/0092-8674(93)90734-8.
Transcription factor p91 contains a SH2 domain and is activated by tyrosine phosphorylation. Here we demonstrate that epidermal growth factor (EGF) induces rapid tyrosine phosphorylation and nuclear translocation of p91. Through its SH2 domain, p91 directly interacts with the EGF receptor in a ligand-dependent manner. p91 is a necessary component of an EGF-induced DNA-binding factor that recognizes a previously identified regulatory element, SIE (c-sis-inducible element), in the c-fos gene promoter. Activated p91 stimulates SIE-dependent transcription in vitro. Cotransfection of an SIE-containing reporter with a p91 expression vector shows that p91 is a positive transcriptional regulator of the c-fos gene promoter. These studies suggest that EGF uses a direct signaling pathway to control nuclear transcriptional events.
转录因子p91含有一个SH2结构域，并通过酪氨酸磷酸化被激活。在此我们证明，表皮生长因子（EGF）可诱导p91迅速发生酪氨酸磷酸化并向细胞核转位。p91通过其SH2结构域以配体依赖的方式直接与EGF受体相互作用。p91是一种EGF诱导的DNA结合因子的必要组成部分，该因子可识别c-fos基因启动子中一个先前已鉴定的调控元件SIE（c-sis诱导元件）。活化的p91在体外可刺激依赖SIE的转录。将含SIE的报告基因与p91表达载体共转染表明，p91是c-fos基因启动子的正向转录调节因子。这些研究提示，EGF利用直接的信号通路来控制细胞核转录事件。
