Growth factor-induced cell division is paralleled by translocation of Gi alpha to the nucleus.
Induction of mitosis by certain growth factors is inhibited by pertussis toxin, indicating that the GTP-binding protein, Gi, is involved in receptor signal transduction to initiate cell division. However, the substrates of receptor-activated Gi that are involved in mitosis have not been determined. The present study has examined whether Gi may directly modulate cell division by receptor-induced subcellular translocation of the alpha subunit of Gi (Gi alpha). Insulin and EGF, particularly when added together or in combination with phorbol dibutyrate (PdBu), induced a rapid (1-4 h) redistribution of Gi alpha from the plasma membrane to perinuclear sites in the cell. After 2 days of stimulation, Gi alpha had translocated into the nucleus of dividing cells and bound specifically to the separating chromatin of dividing nuclei. Unstimulated cells did not display translocation of Gi alpha. This demonstrates a direct involvement of Gi alpha in cell division, which provides an apparently uninterrupted link from growth factor receptor to nucleus.
Crouch
M F
MF
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra.
D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology
D002843:Chromatin; D007328:Insulin; D009227:Myristic Acids; D010455:Peptides; D019814:Myristic Acid; D015240:Phorbol 12,13-Dibutyrate; D004815:Epidermal Growth Factor; D019204:GTP-Binding Proteins