Inactivation of activin-dependent transcription by kinase-deficient activin receptors

Kunihiro Tsuchida, Joan M. Vaughan, Ezra Wiater, Dana Gaddy-Kurtens, Wylie W. Vale

研究成果: Article

64 引用 (Scopus)

抄録

Activin, a member of the transforming growth factor-beta superfamily, binds to two classes of cell surface receptors. These receptors, designated type I and type II, are structurally related members of transmembrane serine kinase superfamily. Antibodies specific for either type I or type II activin receptor can coprecipitate complexes containing both affinity-labeled receptors from activin-responsive cells. Two type I receptors show cell-specific expression and associate with the ligand-binding, type II receptors. To investigate the roles of the cytoplasmic receptor domains in signaling through a heteromeric ligand receptor complex, we have made kinase-deficient activin receptors and correlated their losses in kinase activity with inhibitory effects on an activin-dependent transcriptional response in activin-responsive cell lines. Wild-type activin type II receptors phosphorylate activin type I receptors in transfected COS cells. In contrast, kinase-deficient activin type II receptors fail to phosphorylate type I receptors in transfected COS cells and act as dominant negative mutants to block activin-induced transcriptional activity in both Chinese hamster ovary and K562 (human erythroleukemia) cells. Kinase-deficient activin type IB receptors also block activin-induced transcriptional activity in both Chinese hamster ovary and K562 cells, whereas kinase-deficient activin type I receptors have no effect in either cell line. These results indicate that kinase activities of both type II and type I receptors are required for activin signaling, and that the two type I receptors, which are expressed in a tissue-specific manner, are functionally distinct.

元の言語English
ページ(範囲)5493-5503
ページ数11
ジャーナルEndocrinology
136
発行部数12
DOI
出版物ステータスPublished - 01-01-1995

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Activin Receptors
Activins
Type I Activin Receptors
Type II Activin Receptors
Phosphotransferases
COS Cells
Cricetulus
Ovary
Ligands
Cell Line
Leukemia, Erythroblastic, Acute
K562 Cells
Protein-Serine-Threonine Kinases
Cell Surface Receptors
Cytoplasmic and Nuclear Receptors
Transforming Growth Factor beta
Antibodies

All Science Journal Classification (ASJC) codes

  • Endocrinology

これを引用

Tsuchida, Kunihiro ; Vaughan, Joan M. ; Wiater, Ezra ; Gaddy-Kurtens, Dana ; Vale, Wylie W. / Inactivation of activin-dependent transcription by kinase-deficient activin receptors. :: Endocrinology. 1995 ; 巻 136, 番号 12. pp. 5493-5503.
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abstract = "Activin, a member of the transforming growth factor-beta superfamily, binds to two classes of cell surface receptors. These receptors, designated type I and type II, are structurally related members of transmembrane serine kinase superfamily. Antibodies specific for either type I or type II activin receptor can coprecipitate complexes containing both affinity-labeled receptors from activin-responsive cells. Two type I receptors show cell-specific expression and associate with the ligand-binding, type II receptors. To investigate the roles of the cytoplasmic receptor domains in signaling through a heteromeric ligand receptor complex, we have made kinase-deficient activin receptors and correlated their losses in kinase activity with inhibitory effects on an activin-dependent transcriptional response in activin-responsive cell lines. Wild-type activin type II receptors phosphorylate activin type I receptors in transfected COS cells. In contrast, kinase-deficient activin type II receptors fail to phosphorylate type I receptors in transfected COS cells and act as dominant negative mutants to block activin-induced transcriptional activity in both Chinese hamster ovary and K562 (human erythroleukemia) cells. Kinase-deficient activin type IB receptors also block activin-induced transcriptional activity in both Chinese hamster ovary and K562 cells, whereas kinase-deficient activin type I receptors have no effect in either cell line. These results indicate that kinase activities of both type II and type I receptors are required for activin signaling, and that the two type I receptors, which are expressed in a tissue-specific manner, are functionally distinct.",
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Tsuchida, K, Vaughan, JM, Wiater, E, Gaddy-Kurtens, D & Vale, WW 1995, 'Inactivation of activin-dependent transcription by kinase-deficient activin receptors', Endocrinology, 巻. 136, 番号 12, pp. 5493-5503. https://doi.org/10.1210/endo.136.12.7588300

Inactivation of activin-dependent transcription by kinase-deficient activin receptors. / Tsuchida, Kunihiro; Vaughan, Joan M.; Wiater, Ezra; Gaddy-Kurtens, Dana; Vale, Wylie W.

:: Endocrinology, 巻 136, 番号 12, 01.01.1995, p. 5493-5503.

研究成果: Article

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