spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 10 Jun 2003
doi: 10.1242/jcs.00528

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.00528v1
116/15/3089    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ahmed, C.M. I.
Right arrow Articles by Johnson, H. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ahmed, C.M. I.
Right arrow Articles by Johnson, H. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

The role of IFN{gamma} nuclear localization sequence in intracellular function


C.M. Iqbal Ahmed*, Marjorie A. Burkhart, Mustafa G. Mujtaba, Prem S. Subramaniam, and Howard M. Johnson
* Author for correspondence (e-mail: ahmed1{at}ufl.edu)

Intracellularly expressed interferon {gamma} (IFN{gamma}) has been reported to possess biological activity similar to that of IFN{gamma} added to cells. This study addresses the mechanisms for such similar biological effects. Adenoviral vectors were used to express a non-secreted form of human IFN{gamma} or a non-secreted mutant form in which a previously demonstrated nuclear localization sequence (NLS), 128KTGKRKR134, was replaced with alanines at K and R positions. With the vector expressing non-secreted wild-type IFN{gamma}, biological responses normally associated with extracellular IFN{gamma}, such as antiviral activity and MHC class I upregulation, were observed, although the mutant IFN{gamma} did not possess biological activity. Intracellular human IFN{gamma} possessed biological activity in mouse L cells, which do not recognize extracellularly added human IFN{gamma}. Thus, the biological activity was not due to leakage of IFN{gamma} to the surroundings and subsequent interaction with the receptor on the cell surface. Biological function was associated with activation of STAT1{alpha} and nuclear translocation of IFN{gamma}, IFNGR1 and STAT1{alpha}. Immunoprecipitation of cellular extracts with antibody to the nuclear transporter NPI-1 showed the formation of a complex with IFN{gamma}-IFNGR1-STAT1{alpha}. To provide the physiological basis for these effects we show that extracellularly added IFN{gamma} possesses intracellular signaling activity that is NLS dependent, as suggested by our previous studies, and that this activity occurs via the receptor-mediated endocytosis of IFN{gamma}. The data are consistent with previous observations that the NLS of extracellularly added IFN{gamma} plays a role in IFN{gamma} signaling.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
E. Beurel and R. S. Jope
Differential Regulation of STAT Family Members by Glycogen Synthase Kinase-3
J. Biol. Chem., August 8, 2008; 283(32): 21934 - 21944.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Wang, J. W. Holland, A. Carrington, J. Zou, and C. J. Secombes
Molecular and Functional Characterization of IL-15 in Rainbow Trout Oncorhynchus mykiss: A Potent Inducer of IFN-{gamma} Expression in Spleen Leukocytes
J. Immunol., August 1, 2007; 179(3): 1475 - 1488.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. M. Ahmed, J. P. Martin, and H. M. Johnson
IFN Mimetic as a Therapeutic for Lethal Vaccinia Virus Infection: Possible Effects on Innate and Adaptive Immune Responses
J. Immunol., April 1, 2007; 178(7): 4576 - 4583.
[Abstract] [Full Text] [PDF]

Home page
 CVIHome page
M. G. Mujtaba, C. B. Patel, R. A. Patel, L. O. Flowers, M. A. Burkhart, L. W. Waiboci, J. Martin, M. I. Haider, C. M. Ahmed, and H. M. Johnson
The Gamma Interferon (IFN-{gamma}) Mimetic Peptide IFN-{gamma}(95-133) Prevents Encephalomyocarditis Virus Infection both in Tissue Culture and in Mice.
Clin. Vaccine Immunol., August 1, 2006; 13(8): 944 - 952.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. M. I. Ahmed and H. M. Johnson
IFN-{gamma} and Its Receptor Subunit IFNGR1 Are Recruited to the IFN-{gamma}-Activated Sequence Element at the Promoter Site of IFN-{gamma}-Activated Genes: Evidence of Transactivational Activity in IFNGR1
J. Immunol., July 1, 2006; 177(1): 315 - 321.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
C. M. I. Ahmed, M. A. Burkhart, P. S. Subramaniam, M. G. Mujtaba, and H. M. Johnson
Peptide Mimetics of Gamma Interferon Possess Antiviral Properties against Vaccinia Virus and Other Viruses in the Presence of Poxvirus B8R Protein
J. Virol., May 1, 2005; 79(9): 5632 - 5639.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2003