Cytokines and STAT Signaling

Schindler, Christian; Strehlow, Inga

doi:10.1016/s1054-3589(08)60111-8

Cited by 116 publications

(94 citation statements)

References 382 publications

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“…The N-terminal region of STATs is well Kisseleva et al, 2002). The DNA-binding domain is also highly conserved among the STATs, and all STAT homodimers with the exception of STAT-2 differentially bind more than 10 related g-activated sequence elements that are characterized by the consensus sequence, TTNCNNNAA (Horvath et al, 1995;Xu et al, 1996) Schindler and Strehlow, 2000).…”

Section: Signal Transducers and Activators Of Transcriptionmentioning

confidence: 99%

Hematopoietic cytokine receptor signaling

2007

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Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Proper culmination of these diverse pathways forms the basis for an orderly generation of different cell types. Recent studies conducted over the past 10-15 years have revealed that hematopoietic cytokine receptor signaling is largely mediated by a family of tyrosine kinases termed Janus kinases (JAKs) and their downstream transcription factors termed STATs (signal transducers and activators of transcription). Aberration in these pathways, such as that caused by the recently identified JAK2V617F mutation, is an underlying cause for diseases such as leukemias and other myeloproliferative disorders. This recent discovery, when coupled with the fact that STATs are activated by oncoproteins such as BCR-ABL, underscores the importance of the JAK-STAT pathway in both normal cellular development and disease states.

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Section: Signal Transducers and Activators Of Transcriptionmentioning

confidence: 99%

Hematopoietic cytokine receptor signaling

2007

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“…Activated JAKs phosphorylate the receptor chains, thus creating docking sites for STATs that are in turn tyrosine phosphorylated by JAKs (reviewed in refs. [3][4][5]. In response to IFN-␥, STAT1 is tyrosine phosphorylated at Tyr-701, forms homodimers, translocates to the nucleus, and binds to the ␥-activated sequence (GAS) elements of the target promoters (reviewed in ref.…”

Section: T He Signal Transducer and Activator Of Transcription 1 (Stat1)mentioning

confidence: 99%

p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation

Ramsauer

Sadzak

Porrás

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

119

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“…STAT1 is a key factor not only in signal transduction coupled to IFNAR but also in that coupled to the type II IFN (i.e., IFN-γ) receptor (6). In addition, activation of STAT1 can occur in response to other cytokines, such as IL-6 (14). By contrast, STAT2 is implicated in only IFNAR-coupled signal transduction (6).…”

Section: Introductionmentioning

confidence: 99%

Dysregulated Sonic hedgehog signaling and medulloblastoma consequent to IFN-α–stimulated STAT2-independent production of IFN-γ in the brain

Wang¹,

Pham-Mitchell²,

Schindler³

et al. 2003

J. Clin. Invest.

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The type I IFNs (IFN-α and IFN-β), which are crucial in antiviral defense and immune regulation, signal via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway with activation of STAT1 and STAT2. Here, the function of STAT2 was studied in transgenic mice (termed GIFN/STAT2 -/-) with CNS production of IFN-α. Surprisingly, GIFN/STAT2 -/-, but not GIFN/STAT1-null, transgenic mice, with CNS production of IFN-α, died prematurely with medulloblastoma. An immune response also induced in the brain of the GIFN/STAT2 -/-mice was associated with IFN-γ gene expression by CD3 + T cells and the activation of the STAT1, STAT3, STAT4, and STAT5 molecules. Expression of the Sonic hedgehog (Shh) and the downstream transcriptional factor Gli-1 genes, implicated in the pathogenesis of medulloblastoma, was found to be significantly increased and cotranscribed in cerebellar granule neurons of the GIFN/STAT2 -/-mice. IFN-γ, but not IFN-α, induced STAT1-dependent expression of the Shh gene in cultured cerebellar granule neurons. Thus, there is an unexpected and extraordinarily adverse biological potency of IFN-α in the CNS when the primary signal transduction molecule STAT2 is absent. Moreover, a hitherto unknown role is indicated for the immune system in the pathogenesis of developmental disorders and tumorigenesis of the CNS via dysregulated Shh signaling mediated by IFN-γ.

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Cytokines and STAT Signaling

Cited by 116 publications

References 382 publications

Hematopoietic cytokine receptor signaling

Hematopoietic cytokine receptor signaling

p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation

Dysregulated Sonic hedgehog signaling and medulloblastoma consequent to IFN-α–stimulated STAT2-independent production of IFN-γ in the brain

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