Tyrosine Phosphorylation of DNA Binding Proteins by Multiple Cytokines

Larner, Andrew C.; David, Michael; Igarashi, K; Hackett, R H; Webb, Deborah; Sweitzer, Sharon; Petricoin, Emanuel F.; Finbloom, D S

doi:10.1126/science.8378773

Cited by 358 publications

(167 citation statements)

References 11 publications

(10 reference statements)

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“…STAT proteins can interact with the receptor/tyrosine kinase complex through its SH2 domain [10][11][12]. Many cytokines beside IFNs can activate STAT proteins to regulate gene expression [13][14][15]. In addition to JAK kinase, a variety of tyrosine kinases, such as Src, and EGF receptor tyrosine kinase have been found to activate STAT proteins [16][17][18][19].…”

Section: The Stat Signaling Pathwaymentioning

confidence: 99%

STAT3 in immune responses and inflammatory bowel diseases

2006

Cell Res

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214npg STAT3 has been known as a mediator for gene expression induced by many important cytokines. Recent studies have suggested that STAT3 has important functions in regulation of both innate and adaptive immunity. Loss of STAT3 in immune cells caused severe inflammation in response to pathogens. This review discusses the recent progress and suggests directions for the future research on this interesting molecule.

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Section: The Stat Signaling Pathwaymentioning

confidence: 99%

STAT3 in immune responses and inflammatory bowel diseases

2006

Cell Res

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“…This approach has been successfully used by other groups to characterize proteins binding to GAS-like sequences [12,27]. GAF, the Stat 1 dimer, is present in IFN-y-treated U937 cells and binds to the IFP53-GAS (Fig.…”

Section: Characterization Of Dif By Oligonucleotide Precipitation Andmentioning

confidence: 99%

“…The common denominator of these elements is their ability to bind a dimer of Stat 1, the gamma-interferon activation factor (GAF), [11]. However, GAS-like elements differ slightly in their DNA sequence and are thus capable of specific association with other different Stat proteins [12][13][14][15][16][17][18]. One of these GAS-like elements has originally been found in the promoters of genes that encode milk proteins and that are induced upon prolactin stimulation of mammary gland cells during lactation [19].…”

Section: Introductionmentioning

confidence: 99%

Colony‐stimulating factors and interferon‐γ activate a protein related to MGF‐Stat 5 to cause formation of the differentiation‐induced factor in myeloid cells

et al. 1995

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“…Stat1 and Stat3 are both activated through the EGF receptor (4,6,8,50). Studies using the EGF receptor deletion mutants showed that two intracellular tyrosine residues (Tyr 1068 and Tyr 1086 ) are necessary for Stat activation (51) and may provide binding sites for Stats.…”

Section: Discussionmentioning

confidence: 99%

The Amino Acid Residues Immediately Carboxyl-terminal to the Tyrosine Phosphorylation Site Contribute to Interleukin 6-specific Activation of Signal Transducer and Activator of Transcription 3

Inoue

Minami

Matsumoto

et al. 1997

Journal of Biological Chemistry

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Signal transducers and activators of transcription (Stat) proteins play an important role in signaling through a variety of cytokine and growth factor receptors. Each of the Stat proteins is activated in a ligandspecific manner. Only the Src homology 2 (SH2) domains of Stat1 and Stat2 are critical for the ligand-specific activation of interferon signaling. In this study we determined the domains in Stat3 protein that contribute to interleukin 6 (IL-6)-specific phosphorylation. Based on evidence that Stat3, but not Stat1, is activated in the presence of low levels of IL-6 and soluble IL-6 receptor, we constructed various swap mutants between Stat3 and Stat1 and examined their response to IL-6 after their transient expression into COS7 cells. The region upstream of the SH2 domain was exchangeable between Stat1 and Stat3, whereas the region carboxyl-terminal to the SH2 domain of Stat3 was critical to phosphorylation by IL-6. However, unlike Stat1 and Stat2 in interferon signaling, the swap mutant in which 5 amino acid residues just carboxyl-terminal to the tyrosine phosphorylation site (Tyr 705 ) in Stat3 was replaced by the corresponding region derived from Stat1 was not phosphorylated in response to IL-6. Substituting 1 amino acid (Lys 709 ) at position ؉4 relative to Tyr 705 abolished the tyrosine phosporylation of Stat3 in response to IL-6. Co-immunoprecipitation experiments demonstrated that these mutants were associated with gp130 at an extent similar to wild-type Stat3. Taken together, these results show that the amino acid residues immediately carboxyl-terminal to the tyrosine phosphorylation site are involved in IL-6-specific activation of Stat3.Cytokines and growth factors mediate their biological effects through interaction with their receptors. Investigations into the transcriptional response to interferons have identified the Janus kinases (Jak)-signal transducers and activators of transcription (Stat) 1 signaling pathway, which is in fact used by a large number of cytokines and growth factors (1). The Jak family of known nonreceptor protein kinases consists of Jak1, Jak2, Jak3, and Tyk2. The family of Stat proteins constitutes a new class of transcription factors that contains SH2, SH3-like domains, and a carboxyl-terminal tyrosine phosphorylation site (2). Six Stat family members (Stat1-Stat6) have been cloned. Jak kinases associate with the cytoplasmic membrane proximal region of receptors and are catalytically activated after ligand binding. The activated Jak kinases then phosphorylate Stat proteins at their tyrosine residues. Thereafter, the Stat proteins become homodimerized or heterodimerized and translocate to the nucleus to activate transcription by interaction with specific DNA sequences.The Stat proteins are activated in a ligand-specific manner. In in vitro studies, Stat1 and Stat2 are phosphorylated in response to IFN-␣, whereas Stat1, but not Stat2, is phosphorylated in response to IFN-␥. Besides the IFN signaling systems, Stat1 is activated by signaling through various cytokine receptors...

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Tyrosine Phosphorylation of DNA Binding Proteins by Multiple Cytokines

Cited by 358 publications

References 11 publications

STAT3 in immune responses and inflammatory bowel diseases

STAT3 in immune responses and inflammatory bowel diseases

Colony‐stimulating factors and interferon‐γ activate a protein related to MGF‐Stat 5 to cause formation of the differentiation‐induced factor in myeloid cells

The Amino Acid Residues Immediately Carboxyl-terminal to the Tyrosine Phosphorylation Site Contribute to Interleukin 6-specific Activation of Signal Transducer and Activator of Transcription 3

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