Epidermal growth factor induced tyrosine phosphorylation of nuclear proteins associated with translocation of epidermal growth factor receptor into the nucleus.
Treatment of human squamous carcinoma cells (HN5 cells) with epidermal growth factor (EGF) caused a time-dependent increase in tyrosine phosphorylation of six nuclear proteins of molecular mass 166, 140, 117, 95, 86 and 79 kDa. The major tyrosine phosphorylated protein was indistinguishable from the plasma membrane form of the epidermal growth factor receptor and was shown by enzyme linked immunosorbent assay (ELISA) to be translocated into the nucleus from extra-nuclear sites upon ligand stimulation. Using immunoelectron microscopy of both isolated nuclei and whole cells, epidermal growth factor receptor (EGF-R) was found to be associated with the chromatin and, to a lesser extent, with the inner surface of the nuclear membrane. Tyrosine phosphorylation of proteins other than EGF-R was particularly notable in the nucleoli. These observations suggest that EGF-R may exert some of its physiological functions by directly inducing tyrosine phosphorylation of specific nuclear proteins. Translocation of EGF-R to the nucleus may provide a vital link between plasma membrane signalling and gene activation.
Holt
S J
SJ
CRC Medical Oncology Unit, Southampton General Hospital, U.K.
Alexander
P
P
Inman
C B
CB
Davies
D E
DE
D000595:Amino Acid Sequence; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D000939:Epitopes / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D019000:Phosphotyrosine; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000939:Epitopes; D009687:Nuclear Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors