Type I transforming growth factor β receptor binds to and activates phosphatidylinositol 3-kinase

Youn Yi Jae, Incheol Shin, Carlos L. Arteaga

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

We have examined the interaction of transforming growth factor (TGF) β receptors with phosphatidylinositol 3-(PI3) kinase in epithelial cells. In COS7 cells, treatment with TGFβ increased PI3 kinase activity as measured by the ability of p85-associated immune complexes to phosphorylate inositides in vitro. Both type I and type II TGFβ receptors (TβR) associated with p85, but the association of TβRII appeared to be constitutive. The interaction of TβRI with p85 was induced by treatment with TGFβ. The receptor association with PI3 kinase was not direct as 35S-labeled rabbit reticulocyte p85 did not couple with fusion proteins containing type I and type II receptors. A kinase-dead, dominant-negative mutant of TβRII blocked ligand-induced p85-TβRI association and PI3 kinase activity. In TβRI-null R1B cells, TGFβ did not stimulate PI3 kinase activity. This stimulation was restored upon reconstitution of TβRI by transfection. In R1B and NMuMG epithelial cells, overexpression of a dominant active mutant form of TβRI markedly enhanced ligand-independent PI3 kinase activity, which was blocked by the addition of the TβRI kinase inhibitor LY580278, suggesting a causal link between TβRI function and PI3 kinase. Overexpressed Smad7 also prevented ligand-induced PI3 kinase activity. Taken together, these data suggest that 1) TGFβ receptors can indirectly associate with p85, 2) both receptors are required for ligand-induced PI3 kinase activation, and 3) the activated TβRI serine-threonine kinase can potently induce PI3 kinase activity.

Original languageEnglish (US)
Pages (from-to)10870-10876
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number11
DOIs
StatePublished - Mar 18 2005

Fingerprint

Phosphatidylinositol 3-Kinase
Growth Factor Receptors
Transforming Growth Factors
Phosphatidylinositol 3-Kinases
Ligands
Association reactions
Phosphotransferases
Epithelial Cells
Null Lymphocytes
Protein-Serine-Threonine Kinases
Reticulocytes
Antigen-Antibody Complex
Cell growth
Phosphatidylinositols
Transfection
Fusion reactions
Rabbits
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Type I transforming growth factor β receptor binds to and activates phosphatidylinositol 3-kinase. / Jae, Youn Yi; Shin, Incheol; Arteaga, Carlos L.

In: Journal of Biological Chemistry, Vol. 280, No. 11, 18.03.2005, p. 10870-10876.

Research output: Contribution to journalArticle

@article{a877a18116a743589c6bb2f72daf829d,
title = "Type I transforming growth factor β receptor binds to and activates phosphatidylinositol 3-kinase",
abstract = "We have examined the interaction of transforming growth factor (TGF) β receptors with phosphatidylinositol 3-(PI3) kinase in epithelial cells. In COS7 cells, treatment with TGFβ increased PI3 kinase activity as measured by the ability of p85-associated immune complexes to phosphorylate inositides in vitro. Both type I and type II TGFβ receptors (TβR) associated with p85, but the association of TβRII appeared to be constitutive. The interaction of TβRI with p85 was induced by treatment with TGFβ. The receptor association with PI3 kinase was not direct as 35S-labeled rabbit reticulocyte p85 did not couple with fusion proteins containing type I and type II receptors. A kinase-dead, dominant-negative mutant of TβRII blocked ligand-induced p85-TβRI association and PI3 kinase activity. In TβRI-null R1B cells, TGFβ did not stimulate PI3 kinase activity. This stimulation was restored upon reconstitution of TβRI by transfection. In R1B and NMuMG epithelial cells, overexpression of a dominant active mutant form of TβRI markedly enhanced ligand-independent PI3 kinase activity, which was blocked by the addition of the TβRI kinase inhibitor LY580278, suggesting a causal link between TβRI function and PI3 kinase. Overexpressed Smad7 also prevented ligand-induced PI3 kinase activity. Taken together, these data suggest that 1) TGFβ receptors can indirectly associate with p85, 2) both receptors are required for ligand-induced PI3 kinase activation, and 3) the activated TβRI serine-threonine kinase can potently induce PI3 kinase activity.",
author = "Jae, {Youn Yi} and Incheol Shin and Arteaga, {Carlos L.}",
year = "2005",
month = "3",
day = "18",
doi = "10.1074/jbc.M413223200",
language = "English (US)",
volume = "280",
pages = "10870--10876",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "11",

}

TY - JOUR

T1 - Type I transforming growth factor β receptor binds to and activates phosphatidylinositol 3-kinase

AU - Jae, Youn Yi

AU - Shin, Incheol

AU - Arteaga, Carlos L.

PY - 2005/3/18

Y1 - 2005/3/18

N2 - We have examined the interaction of transforming growth factor (TGF) β receptors with phosphatidylinositol 3-(PI3) kinase in epithelial cells. In COS7 cells, treatment with TGFβ increased PI3 kinase activity as measured by the ability of p85-associated immune complexes to phosphorylate inositides in vitro. Both type I and type II TGFβ receptors (TβR) associated with p85, but the association of TβRII appeared to be constitutive. The interaction of TβRI with p85 was induced by treatment with TGFβ. The receptor association with PI3 kinase was not direct as 35S-labeled rabbit reticulocyte p85 did not couple with fusion proteins containing type I and type II receptors. A kinase-dead, dominant-negative mutant of TβRII blocked ligand-induced p85-TβRI association and PI3 kinase activity. In TβRI-null R1B cells, TGFβ did not stimulate PI3 kinase activity. This stimulation was restored upon reconstitution of TβRI by transfection. In R1B and NMuMG epithelial cells, overexpression of a dominant active mutant form of TβRI markedly enhanced ligand-independent PI3 kinase activity, which was blocked by the addition of the TβRI kinase inhibitor LY580278, suggesting a causal link between TβRI function and PI3 kinase. Overexpressed Smad7 also prevented ligand-induced PI3 kinase activity. Taken together, these data suggest that 1) TGFβ receptors can indirectly associate with p85, 2) both receptors are required for ligand-induced PI3 kinase activation, and 3) the activated TβRI serine-threonine kinase can potently induce PI3 kinase activity.

AB - We have examined the interaction of transforming growth factor (TGF) β receptors with phosphatidylinositol 3-(PI3) kinase in epithelial cells. In COS7 cells, treatment with TGFβ increased PI3 kinase activity as measured by the ability of p85-associated immune complexes to phosphorylate inositides in vitro. Both type I and type II TGFβ receptors (TβR) associated with p85, but the association of TβRII appeared to be constitutive. The interaction of TβRI with p85 was induced by treatment with TGFβ. The receptor association with PI3 kinase was not direct as 35S-labeled rabbit reticulocyte p85 did not couple with fusion proteins containing type I and type II receptors. A kinase-dead, dominant-negative mutant of TβRII blocked ligand-induced p85-TβRI association and PI3 kinase activity. In TβRI-null R1B cells, TGFβ did not stimulate PI3 kinase activity. This stimulation was restored upon reconstitution of TβRI by transfection. In R1B and NMuMG epithelial cells, overexpression of a dominant active mutant form of TβRI markedly enhanced ligand-independent PI3 kinase activity, which was blocked by the addition of the TβRI kinase inhibitor LY580278, suggesting a causal link between TβRI function and PI3 kinase. Overexpressed Smad7 also prevented ligand-induced PI3 kinase activity. Taken together, these data suggest that 1) TGFβ receptors can indirectly associate with p85, 2) both receptors are required for ligand-induced PI3 kinase activation, and 3) the activated TβRI serine-threonine kinase can potently induce PI3 kinase activity.

UR - http://www.scopus.com/inward/record.url?scp=15444372825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15444372825&partnerID=8YFLogxK

U2 - 10.1074/jbc.M413223200

DO - 10.1074/jbc.M413223200

M3 - Article

C2 - 15657037

AN - SCOPUS:15444372825

VL - 280

SP - 10870

EP - 10876

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 11

ER -