HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 48, 34958-34967, November 30, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/48/34958    most recent M704548200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, Y. Articles by Tweardy, D. J. Search for Related Content PubMed PubMed Citation Articles by Huang, Y. Articles by Tweardy, D. J. Social Bookmarking                      What's this?

Stat3 Isoforms, and β, Demonstrate Distinct Intracellular Dynamics with Prolonged Nuclear Retention of Stat3β Mapping to Its Unique C-terminal End^*

Ying Huang, Jihui Qiu, Shuo Dong, Michele S. Redell^¶, Valeria Poli^||, Michael A. Mancini^**, and David J. Tweardy^**1

From the Department of Medicine, Section of Infectious Diseases, ^¶Department of Pediatrics, Section of Hematology/Oncology, and ^**Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, the Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and the ^||Departments of Genetics, Biology, and Biochemistry, University of Turin, Via Nizza 52, Turin 10126, Italy

Two isoforms of Stat3 (signal transducer and activator of transcription 3) are expressed in cells, (p92) and β (p83), both derived from a single gene by alternative mRNA splicing. The 55-residue C-terminal transactivation domain of Stat3 is deleted in Stat3β and replaced by seven unique C-terminal residues (CT7) whose function remains uncertain. We subcloned the open reading frames of Stat3 and Stat3β into the C terminus of green fluorescent protein (GFP). Fluorescent microscopic analysis of HEK293T cells transiently transfected with GFP-Stat3 or GFP-Stat3β revealed similar kinetics and cytokine concentration dependence of nuclear accumulation; these findings were confirmed by high throughput microscope analysis of murine embryonic fibroblasts that lacked endogenous Stat3 but stably expressed either GFP-Stat3 or GFP-Stat3β. However, although time to half-maximal cytoplasmic reaccumulation after cytokine withdrawal was 15 min for GFP-Stat3, it was >180 min for GFP-Stat3β. Furthermore, although the intranuclear mobility of GFP-Stat3 was rapid and increased with cytokine stimulation, the intranuclear mobility of GFP-Stat3β in unstimulated cells was slower than that of GFP-Stat3 in unstimulated cells and was slowed further following cytokine stimulation. Deletion of the unique CT7 domain from Stat3β eliminated prolonged nuclear retention but did not alter its intranuclear mobility. Thus, Stat3 and Stat3β have distinct intracellular dynamics, with Stat3β exhibiting prolonged nuclear retention and reduced intranuclear mobility especially following ligand stimulation. Prolonged nuclear retention, but not reduced intranuclear mobility, mapped to the CT7 domain of Stat3β.

Received for publication, June 4, 2007 , and in revised form, September 10, 2007.

^* This work was supported in part by National Institutes of Health Grant CA72261. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

¹ To whom correspondence should be addressed: Section of Infectious Diseases, Dept. of Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 286, Rm. N1319, Houston, TX 77030. Tel.: 713-798-8918; Fax: 713-798-8948; E-mail: dtweardy{at}bcm.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. E. HANDEL-FERNANDEZ, D. ILKOVITCH, V. IRAGAVARAPU-CHARYULU, L. M. HERBERT, and D. M. LOPEZ Decreased Levels of Both Stat1 and Stat3 in T Lymphocytes from Mice Bearing Mammary Tumors Anticancer Res, June 1, 2009; 29(6): 2051 - 2058. [Abstract] [Full Text] [PDF]

				D. Beysen, L. Moumne, R. Veitia, H. Peters, B. P. Leroy, A. De Paepe, and E. De Baere Missense mutations in the forkhead domain of FOXL2 lead to subcellular mislocalization, protein aggregation and impaired transactivation Hum. Mol. Genet., July 1, 2008; 17(13): 2030 - 2038. [Abstract] [Full Text] [PDF]