de Caestecker M P, Parks W T, Frank C J, Castagnino P, Bottaro D P, Roberts A B, Lechleider R J
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055 USA.
Genes Dev. 1998 Jun 1;12(11):1587-92. doi: 10.1101/gad.12.11.1587.
SMAD proteins mediate signals from receptor serine-threonine kinases (RSKs) of the TGF-beta superfamily. We demonstrate here that HGF and EGF, which signal through RTKs, can also mediate SMAD-dependent reporter gene activation and induce rapid phosphorylation of endogenous SMAD proteins by kinase(s) downstream of MEK1. HGF induces phosphorylation and nuclear translocation of epitope-tagged Smad2 and a mutation that blocks TGF-beta signaling also blocks HGF signal transduction. Smad2 may thus act as a common positive effector of TGF-beta- and HGF-induced signals and serve to modulate cross talk between RTK and RSK signaling pathways.
SMAD蛋白介导来自转化生长因子-β（TGF-β）超家族受体丝氨酸 - 苏氨酸激酶（RSK）的信号。我们在此证明，通过受体酪氨酸激酶（RTK）发出信号的肝细胞生长因子（HGF）和表皮生长因子（EGF），也可介导依赖SMAD的报告基因激活，并通过MEK1下游的激酶诱导内源性SMAD蛋白的快速磷酸化。HGF诱导表位标记的Smad2的磷酸化和核转位，并且阻断TGF-β信号传导的突变也阻断HGF信号转导。因此，Smad2可能作为TGF-β和HGF诱导信号的共同正向效应物，并用于调节RTK和RSK信号通路之间的串扰。
