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The EGF receptor is activated during mitosis and its cell signaling is mediated differently than in interphase (802.13)
Author(s) -
Wee Ping,
Shi Huaiping,
Jiang Jennifer,
Chen Xinmei,
Wang Zhixiang
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.802.13
Subject(s) - interphase , phosphorylation , microbiology and biotechnology , mitosis , nocodazole , epidermal growth factor , signal transduction , chemistry , cell cycle , protein kinase b , epidermal growth factor receptor , mapk/erk pathway , receptor , biology , cell , biochemistry , cytoskeleton
The Epidermal Growth Factor Receptor (EGFR)‐mediated signaling cascades have been intensely studied, especially as to how they relate to many cancers. It has been proposed that the G0 to S interval is the only portion of the cell cycle regulated by the EGF, and that the activation of the EGFR is inhibited during mitosis (M‐phase) so to preserve energy needs required for mitotic structural changes. Here we show that all the major tyrosine residues in the EGFR C‐terminus that are phosphorylated in interphase are also phosphorylated in nocodazole‐induced M‐phase in response to EGF, indicating full activation of EGFR. We further studied EGF‐induced activation of downstream signaling pathways in M‐phase in comparison to interphase. Some signaling proteins such as PLC‐γ1 and CBL are strongly phosphorylated in M‐phase. While two isoforms of AKT were phosphorylated in interphase, only the AKT2 isoform was phosphorylated in M‐phase. p38 MAPK was constitutively phosphorylated in M‐phase regardless of EGF stimulation. Interestingly, ERK1/2 was not phosphorylated in M‐phase. We further showed that the decoupling of ERK1/2 activation from EGFR activation was due to the incomplete activation of RAF‐1. In conclusion, our results demonstrate that in M‐phase, EGF stimulated strong EGFR activation. The activated EGFR is able to selectively activate certain downstream signaling pathways.