Cell-specificity of transforming growth factor-β response is dictated by receptor bioavailability

Magdalena I. Suszko, Teresa K. Woodruff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Members of the transforming growth factor-β (TGFβ) family control diverse cellular responses including differentiation, proliferation, controlled cell death and migration. The response of a cell to an individual ligand is highly restricted yet the signaling pathways for TGFβ, activin and bone morphogenic proteins share a limited number of receptors and activate similar intracellular cytoplasmic co-regulators, Smads. A central question in the study of this family of ligands is how cells titrate and integrate each TGFβ-like signal in order to respond in a cell- and ligand-specific manner. This study uses the pituitary gonadotrope cell line, LβT2, as a model to delineate the relative contribution of TGFβ and activin ligands to follicle-stimulating hormone (FSH) biosynthesis. It was found that pituitary gonadotrope cells do not express the TGFβ type II (TβRII) receptor and are therefore not responsive to the TGFβ ligand. Transfection of the receptor restores TGFβ signaling capabilities and the TGFβ-mediated stimulation of FSHβ gene transcription in LβT2 cells. Consequently, we evaluated the presence of the TβRII in the adult mouse pituitary. TβRII does not co-localize with FSH-producing cells; however it is detected on the cell surface of prolactin- and growth hormone-positive cells. Taken together, these results suggest that the bioavailability of the TGFβ-specific receptor rather than TGFβ dictates pituitary gonadotrope selectivity to activin, which is necessary to maintain normal reproductive function. It is likely that the ligand-restricted mechanisms employed by the gonadotrope are present in other cells, which could explain the distinct control of many cellular processes by members of the TGFβ superfamily.

Original languageEnglish (US)
Pages (from-to)591-600
Number of pages10
JournalJournal of Molecular Endocrinology
Volume36
Issue number3
DOIs
StatePublished - Jun 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Cell-specificity of transforming growth factor-β response is dictated by receptor bioavailability'. Together they form a unique fingerprint.

Cite this