BIOCHEMISTRY Correction for “Mechanism for activation of mutated epidermal growth factor receptors in lung cancer,” by Monica Red Brewer, Cai-Hong Yun, Darson Lai, Mark A. Lemmon, Michael J. Eck, and William Pao, which appeared in issue 38, September 17, 2013, of Proc Natl Acad Sci USA (110:E3595–E3604; first published September 9, 2013; 10.1073/pnas.1220050110).
The authors note that part of the labeling for Fig. 7B appeared incorrectly. The corrected figure and its legend appear below.
Fig. 7.
Lung-cancer–associated EGFRs induce hyperphosphorylation of coexpressed ErbB-2 by virtue of superacceptor activity. (A) Coexpression of lung-cancer–associated mutant ICDs with WT ErbB-2 ICDs in HEK293 cells results in hyperphosphorylation of the ErbB-2–ICD population as assessed by anti–ErbB-2 immunoprecipitation and subsequent Western blotting for anti–ErbB-2–pY1221/22. Coexpression of WT EGFR-ICD with ErbB-2–ICD results in a slight increase in phospho–ErbB-2, whereas coexpression of either lung-cancer–associated ICD (LR or LRTM) with ErbB-2 results in hyperphosphorylation of ErbB-2–ICD (lanes 4, 8, and 12, respectively). Unlike lung-cancer–associated EGFRs containing the donor-enforcing I682Q mutation, combination of lung-cancer–associated EGFR-ICDs containing acceptor-enforcing V924R mutation with ErbB-2–ICD results in hyperphosphorylation of ErbB-2–ICD at levels equivalent to the combination of ErbB-2–ICD with lung-cancer–associated parent EGFR-ICDs (lane 10 compared with lane 8 and lane 14 compared with lane 12). (B) Coexpression of intact WT EGFR with intact ErbB-2 results in an increase in tyrosine-phosphorylated ErbB-2 relative to ErbB-2 expressed alone, whereas ErbB-2 coexpression with lung-cancer–associated mutant EGFR (LRTM) results in a significant increase in phospho-ErbB-2 levels. Treatment of cells coexpressing ErbB-2 and EGFR-L834R/T766M with WZ-4002 in the presence of EGF abrogates the EGFR mutant-induced hyperphosphorylation of ErbB-2 (compare lane 16 to lane 11). A comparatively less dramatic effect on ErbB-2 tyrosine phosphorylation is observed for cells coexpressing ErbB-2 and WT EGFR treated with WZ-4002 in the presence of EGF (compare lane 15 to lane 9). (C) Coexpression of 0.1 μg myc-tagged lung cancer-associated mutant ICD with 1.0 μg of Flag-tagged WT EGFR or ErbB-2–ICD results in additive increases in pAkt or pStat-3 levels compared with singly expressed ICDs, whereas a synergistic increase in pErk levels is observed upon coexpression (compare lanes 2–4 to lanes 6 and 7).