Expression of constitutively-active mutant gs[alpha] (g225t) or
null-mutant of gi[alpha]2 (g203t) induces primitive endoderm from
teratocarcinoma stem cells.
Gao, Ping, David C. Watkins, and Craig C. Malbon.
Department of Molecular Pharmacology, Diabetes & Metabolic Diseases
Research Program, Health Sciences Center, SUNY-Stony Brook, Stony
Brook, NY 11794-8651 USA
APStracts 2:0114C, 1995.
In F9 teratocarcinoma stem cells, retinoic acid induces a primitive
endoderm-like phenotype and a sharp decline in Gi[alpha]2, a response
mimicked by expression of RNA antisense to Gi[alpha]2 in the absence
of this morphogen [Watkins, D. C. et?al. (1992) Science 258: 1373
-1375). The role of the Gs[alpha]/Gi[alpha]2 axis in cellular
differentiation was explored. In the absence of retinoic acid, F9
stem cells stably expressing a constitutively-active mutant of
Gs[alpha] (G225T) progressed to the primitive-endoderm phenotype, as
judged by morphological and differentiation markers, such as tissue
plasminogen activator. Although elevated in cells expressing G225T
Gs[alpha], cyclic AMP does not mimic retinoic acid action and alone
fails to induce stem cells to primitive endoderm. In the absence of
retinoic acid, expression of a null-mutant of Gi[alpha]2 (G203T)
induced stem cells to primitive endoderm also. These observations
establish G-proteins in the Gs[alpha]/Gi[alpha]2 axis as a control
point for regulating progression to primitive endoderm independent of
adenylylcyclase, in this model of early mouse development.
Received 1 August 1994; accepted in final form 20 December 1994,
APS Manuscript Number C453-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 7 March 1995.