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The G‐protein G i regulates mitosis but not DNA synthesis in growth factor‐activated fibroblasts: a role for the nuclear translocation of G i
Author(s) -
Crouch Michael F.,
Simson Ljubov
Publication year - 1997
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.11.2.9039962
Subject(s) - microbiology and biotechnology , g alpha subunit , heterotrimeric g protein , g beta gamma complex , g protein , biology , protein subunit , signal transduction , chemistry , biochemistry , gene
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 G α separating from G βγ . However, we have found a receptor activation of G i 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 G iα binds to chromatin for the duration of mitosis. This report describes the mechanism of G i activation in Swiss 3T3 cells in response to serum, thrombin, and epidermal growth factor, and describes a role for G i2 in the cell cycle. Agonists were found to be unable to induce the physical dissociation of G i2 sub‐units. The α‐ and β‐subunits of G i2 could be coim‐munoprecipitated with a G iα antibody from both the membrane and nuclear fractions of long‐term activated cultures, showing that G iα2 and G iβ are induced to comigrate to the nucleus in response to growth factor receptor activation. G i2 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 G iα to the nucleus induced by either thrombin or EGF may occur without subunit dissociation. Functional studies of the role of G i 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 G i in the induction of cell division by a variety of growth factor receptors. G i 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 G i regulates mitosis but not DNA synthesis in growth factor‐activated fibroblasts: a role for the nuclear translocation of G i . FA‐SEB J. 11, 189‐198(1997)