STAT4

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Signal transducer and activator of transcription 4
Identifiers
Symbols STAT4 ; SLEB11
External IDs OMIM600558 HomoloGene20679 GeneCards: STAT4 Gene
Orthologs
Species Human Mouse
Entrez 6775 20849
Ensembl ENSG00000138378 ENSMUSG00000062939
UniProt Q14765 P42228
RefSeq (mRNA) NM_001243835 NM_001308266
RefSeq (protein) NP_001230764 NP_001295195
Location (UCSC) Chr 2:
191.03 – 191.15 Mb
Chr 1:
51.99 – 52.11 Mb
PubMed search [1] [2]

STAT4 is a transcription factor belonging to the Signal Transducer and Activator of Transcription protein family.[1] It is required for the development of Th1 cells from naive CD4+ T cells[2] and IFN-γ production in response to IL-12.[3]

Structure[edit]

Human as well murine STAT4 genes lie next to STAT1 gene locus suggesting that the genes arose by gene duplication.[1] STAT proteins have several functional domains, including an N-terminal interaction domain, a central DNA-binding domain, an SH2 domain, and the C-terminal transactivation domain.[4]

Expression[edit]

Distribution of STAT4 is restricted to myeloid cells, thymus and testis.[1] In resting human T cells it is expressed at very low levels, but its production is amplified by PHA stimulation.[3]

Activation[edit]

Two chains of IL-12 receptor form heterodimer after IL-12 binding and activate the receptor associated JAK kinases, termed JAK2 and TYK2. Stat4 is phosphorylated by these tyrosine kinases, homodimerizes via its SH2 domain and translocates into nucleus to activate gene transcription.[5]

Target genes[edit]

STAT4 binds to hundreds of sites in the genome,[6] among others to the promoters of genes for cytokines (IFN-γ, TNF), receptors (IL18R1, IL12rβ2, IL18RAP), and signaling factors (MYD88).[6]

References[edit]

  1. ^ a b c Yamamoto K, Quelle FW, Thierfelder WE, Kreider BL, Gilbert DJ, Jenkins NA, Copeland NG, Silvennoinen O, Ihle JN (Jul 1994). "Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation". Molecular and Cellular Biology 14 (7): 4342–9. PMC 358805. PMID 8007943. 
  2. ^ Kaplan MH (2005). "STAT4: a critical regulator of inflammation in vivo". Immunologic Research 31 (3): 231–42. doi:10.1385/IR:31:3:231. PMID 15888914. 
  3. ^ a b Bacon CM, Petricoin EF, Ortaldo JR, Rees RC, Larner AC, Johnston JA, O'Shea JJ (Aug 1995). "Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes". Proceedings of the National Academy of Sciences of the United States of America 92 (16): 7307–11. doi:10.1073/pnas.92.16.7307. PMID 7638186. 
  4. ^ Chang HC, Zhang S, Oldham I, Naeger L, Hoey T, Kaplan MH (Aug 2003). "STAT4 requires the N-terminal domain for efficient phosphorylation". The Journal of Biological Chemistry 278 (34): 32471–7. doi:10.1074/jbc.M302776200. PMID 12805384. 
  5. ^ Wurster AL, Tanaka T, Grusby MJ (May 2000). "The biology of Stat4 and Stat6". Oncogene 19 (21): 2577–84. doi:10.1038/sj.onc.1203485. PMID 10851056. 
  6. ^ a b Good SR, Thieu VT, Mathur AN, Yu Q, Stritesky GL, Yeh N, O'Malley JT, Perumal NB, Kaplan MH (Sep 2009). "Temporal induction pattern of STAT4 target genes defines potential for Th1 lineage-specific programming". Journal of Immunology 183 (6): 3839–47. doi:10.4049/jimmunol.0901411. PMC 2748807. PMID 19710469. 

Further reading[edit]

  • Svenungsson E, Gustafsson J, Leonard D, Sandling J, Gunnarsson I, Nordmark G, Jönsen A, Bengtsson AA, Sturfelt G, Rantapää-Dahlqvist S, Elvin K, Sundin U, Garnier S, Simard JF, Sigurdsson S, Padyukov L, Syvänen AC, Rönnblom L (May 2010). "A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus". Annals of the Rheumatic Diseases 69 (5): 834–40. doi:10.1136/ard.2009.115535. PMID 19762360. 

External links[edit]