Increased expression of Gi alpha 2 in mouse embryo stem cells promotes terminal differentiation to adipocytes
- 1 December 1993
- journal article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 265 (6) , C1729-C1735
- https://doi.org/10.1152/ajpcell.1993.265.6.c1729
Abstract
The level of Gs alpha activity has been shown to modulate the rate of adipogenesis in mouse embryo fibroblast 3T3-L1 cells (H.-Y. Wang, D. C. Watkins, and C. C. Malbon. Nature Lond. 358: 334-337, 1992). For the current work the role of Gi alpha 2, a G protein mediator of inhibitory control of adenylyl cyclase, in regulating terminal differentiation of these cells was explored by stable transfection of fibroblasts expressing wild-type and a constitutively active mutant of Gi alpha 2 (Q205L). Under the influence of the cytomegalovirus promoter, the expression vector yielded a 1.7-fold (Q205L mutant Gi alpha 2) and 2.2-fold (wild-type Gi alpha 2) increase in steady-state levels of these G protein alpha-subunits. Elevation of Gi alpha 2 expression or expression of constitutively active Gi alpha 2 (Q205L) promoted lipid accumulation in these clones, the hallmark of terminal differentiation of 3T3-L1 fibroblasts to adipocytes. Increasing Gi alpha 2 activity promotes adipogenic conversion, as was previously observed by decreasing Gs alpha either by inducers of differentiation or by oligodeoxynucleotides antisense to Gs alpha. Thus Gs alpha and Gi alpha 2 are shown to be counterregulatory with respect to promoting differentiation of 3T3-L1 mouse embryo fibroblasts to adipocytes in the absence of exogenously added inducers of differentiation. This is the first report demonstrating the induction of terminal differentiation of cells by the overexpression of a G protein alpha-subunit, further implicating G proteins as regulators of complex biological responses such as adipogenesis.Keywords
This publication has 3 references indexed in Scilit:
- Signal transduction via the MAP kinases: proceed at your own RSK.Proceedings of the National Academy of Sciences, 1993
- Extracellular signals and reversible protein phosphorylation: What to Mek of it allCell, 1993
- Receptor-effector coupling by G proteinsBiochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, 1990