Cargando…

Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes

Cytokine and growth factor receptor engagement leads to the rapid phosphorylation and activation of latent, cytosolic signal transducers and activators of transcription (STAT) proteins, which then translocate to the nucleus where they regulate transcriptional events from specific promoter sequences....

Descripción completa

Detalles Bibliográficos
Autores principales: Karras, James G., Wang, Zihua, Huo, Li, Howard, Robert G., Frank, David A., Rothstein, Thomas L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196242/
https://www.ncbi.nlm.nih.gov/pubmed/9091577
_version_ 1782148020712767488
author Karras, James G.
Wang, Zihua
Huo, Li
Howard, Robert G.
Frank, David A.
Rothstein, Thomas L.
author_facet Karras, James G.
Wang, Zihua
Huo, Li
Howard, Robert G.
Frank, David A.
Rothstein, Thomas L.
author_sort Karras, James G.
collection PubMed
description Cytokine and growth factor receptor engagement leads to the rapid phosphorylation and activation of latent, cytosolic signal transducers and activators of transcription (STAT) proteins, which then translocate to the nucleus where they regulate transcriptional events from specific promoter sequences. STAT3 expression in particular has been associated with Abl, Src, and HTLV-1 transformation of normal cells. B-1 lymphocytes are self-renewing, CD5(+) B cells that display a propensity for malignant transformation and are the normal counterpart to human chronic lymphocytic leukemias. Further, B-1 cells are characterized by aberrant intracellular signaling, including hyperresponsiveness to phorbol ester PKC agonists. Here we demonstrate that B-1 lymphocytes constitutively express nuclear activated STAT3, which is not expressed by unmanipulated conventional (B-2) lymphocytes. In contrast, STAT3 activation is induced in B-2 cells after antigen receptor engagement in a delayed fashion (after 3 h). Induction of STAT3 is inhibited by both the serine/threonine protein kinase inhibitor H-7 and the immunosuppressive drug rapamycin and requires de novo protein synthesis, demonstrating novel coupling between sIg and STAT proteins that differs from the classical paradigm for STAT induction by cytokine receptors. The inability of prolonged stimulation of conventional B-2 cells with anti-Ig, a treatment sufficient to induce CD5 expression, to result in sustained STAT3 activation suggests that STAT3 is a specific nuclear marker for B-1 cells. Thus, STAT3 may play a role in B cell antigen-specific signaling responses, and its constitutive activation is associated with a normal cell population exhibiting intrinsic proliferative behavior.
format Text
id pubmed-2196242
institution National Center for Biotechnology Information
language English
publishDate 1997
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21962422008-04-16 Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes Karras, James G. Wang, Zihua Huo, Li Howard, Robert G. Frank, David A. Rothstein, Thomas L. J Exp Med Article Cytokine and growth factor receptor engagement leads to the rapid phosphorylation and activation of latent, cytosolic signal transducers and activators of transcription (STAT) proteins, which then translocate to the nucleus where they regulate transcriptional events from specific promoter sequences. STAT3 expression in particular has been associated with Abl, Src, and HTLV-1 transformation of normal cells. B-1 lymphocytes are self-renewing, CD5(+) B cells that display a propensity for malignant transformation and are the normal counterpart to human chronic lymphocytic leukemias. Further, B-1 cells are characterized by aberrant intracellular signaling, including hyperresponsiveness to phorbol ester PKC agonists. Here we demonstrate that B-1 lymphocytes constitutively express nuclear activated STAT3, which is not expressed by unmanipulated conventional (B-2) lymphocytes. In contrast, STAT3 activation is induced in B-2 cells after antigen receptor engagement in a delayed fashion (after 3 h). Induction of STAT3 is inhibited by both the serine/threonine protein kinase inhibitor H-7 and the immunosuppressive drug rapamycin and requires de novo protein synthesis, demonstrating novel coupling between sIg and STAT proteins that differs from the classical paradigm for STAT induction by cytokine receptors. The inability of prolonged stimulation of conventional B-2 cells with anti-Ig, a treatment sufficient to induce CD5 expression, to result in sustained STAT3 activation suggests that STAT3 is a specific nuclear marker for B-1 cells. Thus, STAT3 may play a role in B cell antigen-specific signaling responses, and its constitutive activation is associated with a normal cell population exhibiting intrinsic proliferative behavior. The Rockefeller University Press 1997-03-17 /pmc/articles/PMC2196242/ /pubmed/9091577 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Karras, James G.
Wang, Zihua
Huo, Li
Howard, Robert G.
Frank, David A.
Rothstein, Thomas L.
Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes
title Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes
title_full Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes
title_fullStr Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes
title_full_unstemmed Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes
title_short Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes
title_sort signal transducer and activator of transcription-3 (stat3) is constitutively activated in normal, self-renewing b-1 cells but only inducibly expressed in conventional b lymphocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196242/
https://www.ncbi.nlm.nih.gov/pubmed/9091577
work_keys_str_mv AT karrasjamesg signaltransducerandactivatoroftranscription3stat3isconstitutivelyactivatedinnormalselfrenewingb1cellsbutonlyinduciblyexpressedinconventionalblymphocytes
AT wangzihua signaltransducerandactivatoroftranscription3stat3isconstitutivelyactivatedinnormalselfrenewingb1cellsbutonlyinduciblyexpressedinconventionalblymphocytes
AT huoli signaltransducerandactivatoroftranscription3stat3isconstitutivelyactivatedinnormalselfrenewingb1cellsbutonlyinduciblyexpressedinconventionalblymphocytes
AT howardrobertg signaltransducerandactivatoroftranscription3stat3isconstitutivelyactivatedinnormalselfrenewingb1cellsbutonlyinduciblyexpressedinconventionalblymphocytes
AT frankdavida signaltransducerandactivatoroftranscription3stat3isconstitutivelyactivatedinnormalselfrenewingb1cellsbutonlyinduciblyexpressedinconventionalblymphocytes
AT rothsteinthomasl signaltransducerandactivatoroftranscription3stat3isconstitutivelyactivatedinnormalselfrenewingb1cellsbutonlyinduciblyexpressedinconventionalblymphocytes