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PMID: 11390995 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Biologic consequences of Stat1-independent IFN signaling.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 12 ·2001-06-05 ·Pages 6680-5

Gil MP, Bohn E, O'Guin AK, Ramana CV, Levine B, Stark GR, Virgin HW, Schreiber RD

Abstract

Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNgamma functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNgamma and IFNalpha/beta regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNgamma exerts its Stat1-independent actions on mononuclear phagocytes by regulating the expression of many genes. This result was confirmed by monitoring changes in expression and function of the corresponding gene products. Regulation of the expression of these genes requires the IFNgamma receptor and Jak1. The physiologic relevance of IFN-dependent, Stat1-independent signaling was demonstrated by monitoring antiviral responses in Stat1-null mice. Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences.

MeSH Terms
Animals Cell Division/drug effects DNA-Binding Proteins/physiology Gene Expression Regulation/drug effects Humans Interferons/pharmacology Janus Kinase 1 Macrophages/metabolism Mice Protein-Tyrosine Kinases/physiology Receptors, Interferon/physiology STAT1 Transcription Factor Trans-Activators/physiology
Chemicals
DNA-Binding Proteins Receptors, Interferon STAT1 Transcription Factor STAT1 protein, human Stat1 protein, mouse Trans-Activators interferon gamma receptor Interferons Protein-Tyrosine Kinases JAK1 protein, human Jak1 protein, mouse Janus Kinase 1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gil M P
Department of Pathology and Immunology, Center for Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Bohn E
O'Guin A K
Ramana C V
Levine B
Stark G R
Virgin H W
Schreiber R D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.111163898
Published
2001-06-05
Pages
6680-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC34412
Subset
IM
Grants
NIAID NIH HHS · AI44157 · United States
NIAID NIH HHS · AI39616 · United States
NCI NIH HHS · R37 CA043059 · United States
NCI NIH HHS · CA43059 · United States
NCI NIH HHS · R01 CA043059 · United States
NCI NIH HHS · CA62220 · United States
NCI NIH HHS · P01 CA062220 · United States
External Links
PubMed source DOI: 10.1073/pnas.111163898 PMC Full Text View journal details
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