The G‐protein Gi regulates mitosis but not DNA synthesis in growth factor‐activated fibroblasts: a role for the nuclear translocation of Gi

• Published in: The FASEB journal 1997-02, Vol.11 (2), p.189-198
• Main Authors: Crouch, Michael F., Simson, Ljubov
• Format: Article
• Language: English
• Subjects: EGF cellular proliferation; immunoprecipitation; nuclear fraction; β‐subunit
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.11.2.9039962

GTP binding proteins, heterotri‐meric molecules composed of α‐,β‐, and γ‐subunits, are known to serve as transducers of information from seven‐transmembrane receptors. Activation of G‐proteins has been generally considered to involve subunit dissociation, with Gα separating from Gβγ. However, we have found a receptor activation of Gi in proliferating cells that differs from these models and involves the subcellular translocation of the α‐subunit from the cell periphery to the nucleus where Giα binds to chromatin for the duration of mitosis. This report describes the mechanism of Gi activation in Swiss 3T3 cells in response to serum, thrombin, and epidermal growth factor, and describes a role for Gi2 in the cell cycle. Agonists were found to be unable to induce the physical dissociation of Gi2 sub‐units. The α‐ and β‐subunits of Gi2 could be coim‐munoprecipitated with a Giα antibody from both the membrane and nuclear fractions of long‐term activated cultures, showing that Giα2 and Giβ are induced to comigrate to the nucleus in response to growth factor receptor activation. Gi2 appears to be activated in part by a postreceptor signal that can be mimicked by protein kinase C activation; this signal may be responsible for the convergence of the signaling mechanisms of these distinct seven‐transmembrane and tyrosine kinase receptors. We suggest that translocation of Giα to the nucleus induced by either thrombin or EGF may occur without subunit dissociation. Functional studies of the role of Gi showed that pertussis toxin does not block DNA synthesis in Swiss 3T3 fibroblasts induced by serum or thrombin, but that cell proliferation is retarded to each. These results provide direct evidence for a novel mechanism of GTP binding protein activation and for an essential role of Gi in the induction of cell division by a variety of growth factor receptors. Gi can carry out this role in control of cellular proliferation through its translocation to the nucleus of mitotic cells.—Crouch, M. F., Simeon, L. The G‐protein Gi regulates mitosis but not DNA synthesis in growth factor‐activated fibroblasts: a role for the nuclear translocation of Gi. FA‐SEB J. 11, 189‐198(1997)