Premium
Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c‐erbB‐2 receptor via epidermal growth factor receptor
Author(s) -
Dittmar Thomas,
Husemann Anja,
Schewe Yvonne,
Nofer JerzyRoch,
Niggemann Bernd,
Zänker Kurt S.,
Brandt Burkhard H.
Publication year - 2002
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/fj.02-0096fje
Subject(s) - tyrosine phosphorylation , epidermal growth factor , erbb , microbiology and biotechnology , phosphorylation , cancer research , receptor tyrosine kinase , tyrosine kinase , chemistry , epidermal growth factor receptor , biology , signal transduction , receptor , biochemistry
Induction of tumor cell migration is a key step in invasion and metastasis. Here we report that the epidermal growth factor (EGF)‐induced cell migration of breast cancer cells is attributed to a transient, rather than a sustained, activation of phospholipase C (PLC) ‐γ1 due to c‐erbB‐2 signaling. EGF stimulation of EGF receptor (EGFR) overexpressing cells resulted in long‐term PLC‐γ1 tyrosine phosphorylation and sustained levels of inositol‐1,4,5‐triphosphate (IP 3 ) and diacylglycerol (DAG) producing sinusoidal calcium oscillations. In contrast, c‐erbB‐2/EGFR expressing cells displayed baseline transient calcium oscillations after EGF treatment due to short‐term PLC‐γ1 tyrosine phosphorylation and short‐term IP 3 and DAG turnover. A third cell line expressing a point‐mutated c‐erbB‐2 receptor that lacks the autophosphorylation Y1248 was generated to investigate whether the different PLC‐γ1 activation was attributed to this structure. Neither PLC‐γ1 tyrosine phosphorylation nor IP 3 and DAG turnover and calcium oscillations were observed in this cell line, indicating the modulation of the PLC‐γ1 activation time course by c‐erbB‐2 signaling. Induction of cell migration was solely observable in the c‐erbB‐2‐positive cell line as proved by the mode of actin reorganization and a cell migration assay, using a 3D‐ collagen lattice. In summary, c‐erbB‐2 up‐regulation switches on the cell migration program by modulating the time course of PLC‐γ1 activation.