Valgeirsdóttir S, Paukku K, Silvennoinen O, Heldin C H, Claesson-Welsh L
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Oncogene. 1998 Jan 29;16(4):505-15. doi: 10.1038/sj.onc.1201555.
Signal transducers and activators of transcription (Stats) are known to transduce signals from the cell surface to the nucleus in cytokine receptor signaling. We examined the capacity of platelet-derived growth factor (PDGF) receptor to interact with and activate Stat molecules. Activation of the PDGF beta-receptor led to tyrosine phosphorylation of Stat1, Stat3 and Stat5, which was accompanied by specific DNA-binding activities. These events were only weakly stimulated by the activated PDGF alpha-receptor. In cells expressing PDGF beta-receptors mutated at Tyr579, Tyr581 or Tyr775, tyrosine phosphorylation as well as DNA-binding activity of Stat5 was reduced. Immobilized peptides containing phosphorylated Tyr579, Tyr581 or Tyr775 bound Stat5, suggesting direct binding of Stat5 to these tyrosine residues of the PDGF beta-receptor. Members of the Janus kinase family were also shown to interact with the PDGF beta-receptor, and to a lesser extent with the alpha-receptor, but their importance for PDGF-induced Stat activation remains to be determined.
已知信号转导子和转录激活子（Stats）在细胞因子受体信号传导中可将信号从细胞表面转导至细胞核。我们研究了血小板衍生生长因子（PDGF）受体与Stat分子相互作用并激活Stat分子的能力。PDGFβ受体的激活导致Stat1、Stat3和Stat5的酪氨酸磷酸化，并伴有特异性DNA结合活性。这些事件仅受到激活的PDGFα受体的微弱刺激。在Tyr579、Tyr581或Tyr775发生突变的表达PDGFβ受体的细胞中，Stat5的酪氨酸磷酸化以及DNA结合活性降低。含有磷酸化Tyr579、Tyr581或Tyr775的固定化肽可结合Stat5，这表明Stat5可直接结合至PDGFβ受体的这些酪氨酸残基。还显示Janus激酶家族成员可与PDGFβ受体相互作用，与α受体的相互作用程度较小，但其对PDGF诱导的Stat激活的重要性仍有待确定。
