TY - JOUR
T1 - Mitogenic effects of pertussis toxin-sensitive G-protein α subunits
T2 - The mitogenic action of αi2 in NIH 3T3 cells is mimicked by αi1, but not αi3
AU - Hermouet, Sylvie
AU - de Mazancourt, Philippe
AU - Spiegel, Allen M.
PY - 1993/3
Y1 - 1993/3
N2 - In fibroblasts and other cell types, pertussis toxin (PTX) inhibits DNA synthesis in response to serum and certain growth factors. GTPase deficient forms of the PTX-sensitive G-protein αi2 subunit have been shown to induce partial transformation in fibroblasts. In order to determine whether other PTX-sensitive G-protein scan stimulate mitogenic pathways, we stably expressed constitutively activated G-protein αi1 and αi3 subunits in NIH 3T3 cells. Expression of activated αi1, αi2 or αi3 results in inhibition of forskolin-stimulated cAMP accumulation in intact cells. Constitutively activated αi1, but not αi3, induces a loss of contact inhibition, a loss of anchorage-dependence, a reduced serum requirement and a decreased doubling time in NIH 3T3 cells. We conclude that αi1 and αi2 are both capable of transducing mitogenic signals, but that αi3 is not involved in the regulation of fibroblast growth. Furthermore, adenylyl cyclase inhibition is clearly not sufficient to explain the effect of αi2 on fibroblast growth.
AB - In fibroblasts and other cell types, pertussis toxin (PTX) inhibits DNA synthesis in response to serum and certain growth factors. GTPase deficient forms of the PTX-sensitive G-protein αi2 subunit have been shown to induce partial transformation in fibroblasts. In order to determine whether other PTX-sensitive G-protein scan stimulate mitogenic pathways, we stably expressed constitutively activated G-protein αi1 and αi3 subunits in NIH 3T3 cells. Expression of activated αi1, αi2 or αi3 results in inhibition of forskolin-stimulated cAMP accumulation in intact cells. Constitutively activated αi1, but not αi3, induces a loss of contact inhibition, a loss of anchorage-dependence, a reduced serum requirement and a decreased doubling time in NIH 3T3 cells. We conclude that αi1 and αi2 are both capable of transducing mitogenic signals, but that αi3 is not involved in the regulation of fibroblast growth. Furthermore, adenylyl cyclase inhibition is clearly not sufficient to explain the effect of αi2 on fibroblast growth.
KW - Fibroblasts
KW - PTX-sensitive G-proteins
KW - proliferation
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U2 - 10.1016/0898-6568(93)90072-T
DO - 10.1016/0898-6568(93)90072-T
M3 - Article
C2 - 8388703
AN - SCOPUS:0027414458
SN - 0898-6568
VL - 5
SP - 215
EP - 225
JO - Cellular Signalling
JF - Cellular Signalling
IS - 2
ER -