The phosphatidylinositol 3-kinase/Akt signaling pathway modulates the endocrine differentiation of trophoblast cells

Takayuki Kamei, Stephanie R. Jones, Belinda M. Chapman, Kerry L Kreidel, Guoli Dai, Michael J. Soares

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Activation of Lyn, a Src-related nonreceptor tyrosine kinase, in trophoblast cells is associated with trophoblast giant cell differentiation. The purpose of the present work was to use Lyn as a tool to identify signaling pathways regulating the endocrine differentiation of trophoblast cells. The Src homology 3 domain of Lyn was shown to display differentiation-dependent associations with other regulatory proteins, including phosphatidylinositol 3-kinase (PI3-K). PI3-K activation was dependent upon trophoblast giant cell differentiation. The downstream mediator of PI3-K, Akt/protein kinase B, also exhibited differentiation-dependent activation. Lyn is a potential regulator of the PI3-K/Akt signaling pathway, as are receptor tyrosine kinases. Protein tyrosine kinase profiling was used to identify two candidate regulators of the PI3-K/Akt pathway, fibroblast growth factor receptor-1 and Sky. At least part of the activation of Akt in differentiating trophoblast giant cells involves an autocrine growth arrest-specific-6-Sky signaling pathway. Inhibition of PI3-K activities via treatment with LY294002 disrupted Akt activation and interfered with the endocrine differentiation of trophoblast giant cells. In summary, activation of the PI3-K/Akt signaling pathway regulates the development of the differentiated trophoblast giant cell phenotype.

Original languageEnglish (US)
Pages (from-to)1469-1481
Number of pages13
JournalMolecular Endocrinology
Volume16
Issue number7
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Trophoblasts
Cell Differentiation
Giant Cells
Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 1
Proto-Oncogene Proteins c-akt
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
src Homology Domains
Receptor Protein-Tyrosine Kinases
Phenotype
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

The phosphatidylinositol 3-kinase/Akt signaling pathway modulates the endocrine differentiation of trophoblast cells. / Kamei, Takayuki; Jones, Stephanie R.; Chapman, Belinda M.; Kreidel, Kerry L; Dai, Guoli; Soares, Michael J.

In: Molecular Endocrinology, Vol. 16, No. 7, 01.01.2002, p. 1469-1481.

Research output: Contribution to journalArticle

Kamei, Takayuki ; Jones, Stephanie R. ; Chapman, Belinda M. ; Kreidel, Kerry L ; Dai, Guoli ; Soares, Michael J. / The phosphatidylinositol 3-kinase/Akt signaling pathway modulates the endocrine differentiation of trophoblast cells. In: Molecular Endocrinology. 2002 ; Vol. 16, No. 7. pp. 1469-1481.
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