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. Author manuscript; available in PMC: 2021 Sep 22.
Published in final edited form as: Mol Cancer Res. 2020 Feb 6;18(5):774–786. doi: 10.1158/1541-7786.MCR-18-1370

Figure 5.

Figure 5.

c-Src–mediated tyrosine 1455 phosphorylation regulates CIC nuclear export. A, HEK293 cells transfected with indicated plasmids were lysed and nuclear or cytoplasmic fractions were obtained and immunoblotted with indicated antibodies. B, U87 cells stably expressing CIC-FLAG(WT) transfected with indicated plasmids were lysed and nuclear or cytoplasmic fractions were obtained and immunoblotted with indicated antibodies. C, HEK293 parental cells or endogenously tagged with HA-CIC pretreated for 1 hour with either PD98509 or dasatinib prior to treatment with or without EGF were lysed and nuclear or cytoplasmic fractions were obtained and immunoblotted with indicated antibodies. D, MEFs or Src(−/−) MEFs treated with or without EGF were lysed and nuclear or cytoplasmic fractions obtained and immunoblotted with indicated antibodies. E and F, HEK293 cells transfected with indicated plasmids were lysed and nuclear or cytoplasmic fractions were obtained and immunoblotted with indicated antibodies. G, GSC 7-2 stably expressing FLAG-CIC(WT or Y1455F) treated with or without EGF were lysed and nuclear or cytoplasmic fractions were obtained and immunoblotted with indicated antibodies. H, Diagram depicting two parallel mechanism that regulate CIC function upon EGFR activation, the c-Src–mediated phosphorylation of tyrosine 1455 residue of nuclear CIC that is not DNA bound and ERK-mediated serine phosphorylation and degradation of DNA-bound CIC. Ctr, control.