Volume 272, Number 39,
Issue of September 26, 1997
pp. 24461-24467
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
G
12 and G13 Mediate Differentiation
of P19 Mouse Embryonal Carcinoma Cells in Response to Retinoic
Acid
(Received for publication, April 15, 1997, and in revised form, June 18, 1997)
Eek-Hoon
Jho
and
Craig C.
Malbon
From the Department of Molecular Pharmacology, Diabetes & Metabolic
Diseases Research Center, School of Medicine, State University of New
York, Stony Brook, New York 11794-8651
P19 mouse embryonal carcinoma cells can be
stimulated to differentiate into endodermal-like, mesodermal-like, and
neuronal-like phenotypes in response to specific morphogens. At low
concentrations, retinoic acid stimulates P19 embryonal cells to
differentiate to cells displaying an endodermal phenotype, whereas at
higher concentrations it stimulates differentiation to neuroectoderm. The G
12 and G13 subunits of
heterotrimeric G-proteins are expressed in the embryonal P19 cells and
stimulated in response to retinoic acid as the cells differentiate to
endodermal or neuroectodermal phenotypes. Suppression of the expression
of either G12 or G13 by antisense RNA is
shown to promote cell detachment from substratum and apoptosis.
Expression of the constitutively active, mutant form of
G12 (Q229L), in contrast, stimulates loss of the
embryonal phenotype. Expression of the constitutively active form of
G13 (Q226L) stimulates differentiation of the cells from
embryonal to endodermal, in the absence of retinoic acid. Thus, both
G12 and G13 are essential to stimulation
of cell differentiation by retinoic acid. Deficiency of either
G12 or G13 increases programmed cell
death.
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