Inhibition of DNA synthesis in living cells by microinjection of Gi2 antibodies.
Heterotrimeric guanine nucleotide binding proteins function in the coupling of a diverse span of cell surface receptors to a variety of intracellular signaling pathways, some of which stimulate cellular proliferation. With the recent discovery that mutated forms of G proteins are present in specific tumors, there has been an increased interest in the determination of the role of specific subtypes of G proteins in the regulation of cellular growth. We have attempted to determine which subtypes of G proteins are directly involved in serum-stimulated DNA synthesis through microinjection of inhibitory antibodies into living cells. Inhibitory rabbit polyclonal antibodies directed against specific Gi alpha subunits were introduced into living Balb/c 3T3 fibroblasts by microinjection, and the effect upon serum-stimulated DNA synthesis was examined. Results of these experiments indicate that Gi2 plays a direct role in serum-stimulated DNA synthesis in living cells and suggest that G proteins may function in a variety of mitogenic signaling pathways initiated by serum growth factors.
LaMorte
V J
VJ
Department of Pharmacology, University of California, San Diego, La Jolla 92093.
Goldsmith
P K
PK
Spiegel
A M
AM
Meinkoth
J L
JL
Feramisco
J R
JR
D016475:3T3 Cells; D000818:Animals; D001769:Blood; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D008856:Microscopy, Fluorescence; D010982:Platelet-Derived Growth Factor / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D004247:DNA; D019204:GTP-Binding Proteins