FKBP12 is not required for the modulation of transforming growth factor β receptor I signaling activity in embryonic fibroblasts and thymocytes

Craig H. Bassing, Weinian Shou, Scott Muir, Joseph Heitman, Martin M. Matzuk, Xiao Fan Wang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Transforming growth factor β (TGF-β) signals through a heteromeric complex of type I and type II transmembrane serine-threonine kinases. Recent evidence suggests that the immunophilin FKBP12 modulates the activity of the type I receptor, based on data that immunosuppressive drugs that disrupt FKBP12 binding to the type I receptor enhance TGF-β signaling in mink lung epithelial cells, and overexpression of FKBP12 inhibits type I receptor phosphorylation by the type II receptor. To determine the physiological relevance of the FKBP12-TGF-β receptor I interaction, we investigated whether disruption of this interaction affects TGF-β-signaling in primary mouse embryo fibroblasts and thymocytes. We found that the addition of excess drugs had no effect on either TGF-β-mediated transcriptional responses or growth inhibition. Dose-response curves for TGF-β-mediated signaling in primary fibroblasts and thymocytes isolated from either wild-type or FKBP12- deficient mice were identical. Taken together, our results indicate that FKBP12 does not play a unique physiological role in TGF-β signaling in primary fibroblasts and thymocytes.

Original languageEnglish (US)
Pages (from-to)223-228
Number of pages6
JournalCell Growth and Differentiation
Volume9
Issue number3
StatePublished - 1998
Externally publishedYes

Fingerprint

Tacrolimus Binding Protein 1A
Growth Factor Receptors
Transforming Growth Factors
Thymocytes
Fibroblasts
Immunophilins
Mink
Protein-Serine-Threonine Kinases
Immunosuppressive Agents
Pharmaceutical Preparations
Embryonic Structures
Epithelial Cells
Phosphorylation
Lung

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

FKBP12 is not required for the modulation of transforming growth factor β receptor I signaling activity in embryonic fibroblasts and thymocytes. / Bassing, Craig H.; Shou, Weinian; Muir, Scott; Heitman, Joseph; Matzuk, Martin M.; Wang, Xiao Fan.

In: Cell Growth and Differentiation, Vol. 9, No. 3, 1998, p. 223-228.

Research output: Contribution to journalArticle

Bassing, Craig H. ; Shou, Weinian ; Muir, Scott ; Heitman, Joseph ; Matzuk, Martin M. ; Wang, Xiao Fan. / FKBP12 is not required for the modulation of transforming growth factor β receptor I signaling activity in embryonic fibroblasts and thymocytes. In: Cell Growth and Differentiation. 1998 ; Vol. 9, No. 3. pp. 223-228.
@article{c3b0bbac83fc4a528f7c5aa38a3d0b4a,
title = "FKBP12 is not required for the modulation of transforming growth factor β receptor I signaling activity in embryonic fibroblasts and thymocytes",
abstract = "Transforming growth factor β (TGF-β) signals through a heteromeric complex of type I and type II transmembrane serine-threonine kinases. Recent evidence suggests that the immunophilin FKBP12 modulates the activity of the type I receptor, based on data that immunosuppressive drugs that disrupt FKBP12 binding to the type I receptor enhance TGF-β signaling in mink lung epithelial cells, and overexpression of FKBP12 inhibits type I receptor phosphorylation by the type II receptor. To determine the physiological relevance of the FKBP12-TGF-β receptor I interaction, we investigated whether disruption of this interaction affects TGF-β-signaling in primary mouse embryo fibroblasts and thymocytes. We found that the addition of excess drugs had no effect on either TGF-β-mediated transcriptional responses or growth inhibition. Dose-response curves for TGF-β-mediated signaling in primary fibroblasts and thymocytes isolated from either wild-type or FKBP12- deficient mice were identical. Taken together, our results indicate that FKBP12 does not play a unique physiological role in TGF-β signaling in primary fibroblasts and thymocytes.",
author = "Bassing, {Craig H.} and Weinian Shou and Scott Muir and Joseph Heitman and Matzuk, {Martin M.} and Wang, {Xiao Fan}",
year = "1998",
language = "English (US)",
volume = "9",
pages = "223--228",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - FKBP12 is not required for the modulation of transforming growth factor β receptor I signaling activity in embryonic fibroblasts and thymocytes

AU - Bassing, Craig H.

AU - Shou, Weinian

AU - Muir, Scott

AU - Heitman, Joseph

AU - Matzuk, Martin M.

AU - Wang, Xiao Fan

PY - 1998

Y1 - 1998

N2 - Transforming growth factor β (TGF-β) signals through a heteromeric complex of type I and type II transmembrane serine-threonine kinases. Recent evidence suggests that the immunophilin FKBP12 modulates the activity of the type I receptor, based on data that immunosuppressive drugs that disrupt FKBP12 binding to the type I receptor enhance TGF-β signaling in mink lung epithelial cells, and overexpression of FKBP12 inhibits type I receptor phosphorylation by the type II receptor. To determine the physiological relevance of the FKBP12-TGF-β receptor I interaction, we investigated whether disruption of this interaction affects TGF-β-signaling in primary mouse embryo fibroblasts and thymocytes. We found that the addition of excess drugs had no effect on either TGF-β-mediated transcriptional responses or growth inhibition. Dose-response curves for TGF-β-mediated signaling in primary fibroblasts and thymocytes isolated from either wild-type or FKBP12- deficient mice were identical. Taken together, our results indicate that FKBP12 does not play a unique physiological role in TGF-β signaling in primary fibroblasts and thymocytes.

AB - Transforming growth factor β (TGF-β) signals through a heteromeric complex of type I and type II transmembrane serine-threonine kinases. Recent evidence suggests that the immunophilin FKBP12 modulates the activity of the type I receptor, based on data that immunosuppressive drugs that disrupt FKBP12 binding to the type I receptor enhance TGF-β signaling in mink lung epithelial cells, and overexpression of FKBP12 inhibits type I receptor phosphorylation by the type II receptor. To determine the physiological relevance of the FKBP12-TGF-β receptor I interaction, we investigated whether disruption of this interaction affects TGF-β-signaling in primary mouse embryo fibroblasts and thymocytes. We found that the addition of excess drugs had no effect on either TGF-β-mediated transcriptional responses or growth inhibition. Dose-response curves for TGF-β-mediated signaling in primary fibroblasts and thymocytes isolated from either wild-type or FKBP12- deficient mice were identical. Taken together, our results indicate that FKBP12 does not play a unique physiological role in TGF-β signaling in primary fibroblasts and thymocytes.

UR - http://www.scopus.com/inward/record.url?scp=0031879342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031879342&partnerID=8YFLogxK

M3 - Article

VL - 9

SP - 223

EP - 228

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 3

ER -