12 and Gα13 mediate differentiation of P19 mouse embryonal carcinoma cells in response to retinoic acid

Eek Hoon Jho, Craig C. Malbon

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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 Gα12 and Gα13 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 Gα12 or Gα13 by antisense RNA is shown to promote cell detachment from substratum and apoptosis. Expression of the constitutively active, mutant form of Gα12 (Q229L), in contrast, stimulates loss of the embryonal phenotype. Expression of the constitutively active form of Gα13 (Q226L) stimulates differentiation of the cells from embryonal to endodermal, in the absence of retinoic acid. Thus, both Gα12 and Gα13 are essential to stimulation of cell differentiation by retinoic acid. Deficiency of either G∅12 or Gα13 increases programmed cell death.

Original languageEnglish
Pages (from-to)24461-24467
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number39
DOIs
StatePublished - 26 Sep 1997

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