Maximal activation of transcription by statl and stat3 requires both tyrosine and serine phosphorylation

  title={Maximal activation of transcription by statl and stat3 requires both tyrosine and serine phosphorylation},
  author={Zilong Wen and Zhong Zhong and James E. Darnell},

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STATs in Cytokine-mediated Transcriptional Regulation
The current understanding of the functional domains, the regulation, and the physiological roles of STATs in cytokine signaling are reviewed.
Serine phosphorylation of STATs
This review addresses recent advances in understanding the regulation of STAT serine phosphorylation, as well as the kinases and other signal transducers implied in this process.
Serine Phosphorylation and Negative Regulation of Stat3 by JNK*
It is demonstrated that JNK1, activated by its upstream kinase MKK7, negatively regulated the tyrosine phosphorylation and DNA binding and transcriptional activities of Stat3 stimulated by EGF and pretreatment of cells with UV reduced the EGF-stimulated tyrosining and phosphotyrosine-dependent activities of stat3.
JAKs and STATs branch out.
CDK8 as the STAT1 serine 727 kinase?
The authors state that the CDK8 module of the Mediator complex is a key component in the STAT1 signal pathway, linking serine phosphorylation to gene-specific transcriptional events.
Stat1 serine phosphorylation occurs independently of tyrosine phosphorylation and requires an activated Jak2 kinase
Evidence is presented that Stat1 tyrosineosphorylation is not a prerequisite for Stat1 serine phosphorylation, although an active Jak2 kinase is required for both phosphorylated events.
STAT3 Is a Serine Kinase Target in T Lymphocytes
The results show that STAT3 proteins are targets for multiple kinase pathways in T cells and can integrate signals from both cytokine receptors and antigen receptors, and it is shown that H-7-sensitive kinases do not regulate STAT3 tyrosine phosphorylation or phosphorylated of serine 727.
Regulation of Stat3 Activation by MEK Kinase 1*
A novel role of MEKK1 to modulate tyrosine kinases that results in the activation of specific members of STAT family is demonstrated for the first time.
Simultaneous tyrosine and serine phosphorylation of STAT3 transcription factor is involved in Rho A GTPase oncogenic transformation.
Results indicate that Stat3 is an important player in RhoA-mediated oncogenic transformation, which requires simultaneous phosphorylation at both tyrosine and serine residues by specific signaling events triggered by Rho a effectors.


Requirement of serine phosphorylation for formation of STAT-promoter complexes.
Serine phosphorylation appears to enhance or to be required for the formation of stable Stat3-Stat3, a member of the interleukin-6 family of cytokines, which binds to and activate receptors that contain a common subunit, gp130.
A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma.
Interferon-gamma (IFN-gamma) stimulates transcription of specific genes by inducing tyrosine phosphorylation of a 91-kilodalton cytoplasmic protein (termed STAT for signal transducer and activator of
Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6.
A new family member, Stat3, becomes activated through phosphorylation on tyrosine as a DNA binding protein in response to epidermal growth factor and interleukin-6 but not interferon gamma (IFN-gamma).
Tyrosine-phosphorylated Stat1 and Stat2 plus a 48-kDa protein all contact DNA in forming interferon-stimulated-gene factor 3.
Evidence is presented that a heterodimer of Stat1 and Stat2 is present in ISGF3 and that Stat 1 and the 48-kDa protein make precise contact, while Stat2 makes general contact, with the interferon-stimulated response element, the binding site of the IsGF3.
Transcription factor ISGF-3 formation requires phosphorylated Stat91 protein, but Stat113 protein is phosphorylated independently of Stat91 protein.
Using cell lines lacking the Stat91 or Stat84 proteins, it is shown that mutations in several different sites in the 91-kDa protein block the interferon alpha-induced phosphorylation of the 91/84 protein and subsequent ISGF-3 formation.
Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins
The tyrosine phosphorylation events on Stat and Jak proteins after treatment of cells with IFNs α and γ and with epidermal growth factor (EGF) are investigated and Jakl is found to be the enzyme that phosphorylates Tyr701inStat91.
Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor.
The interferon-alpha-stimulated gene factor 3 (ISGF3), a transcriptional activator, contains three proteins that reside in the cell cytoplasm until they are activated in response to IFN-alpha, and may link occupation of a specific polypeptide receptor with activation of transcription of a set of specific genes.
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.
A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Stat3 and Stat4: members of the family of signal transducers and activators of transcription.
Comparison with the deduced protein sequence of the two previously described genes (Stat91 and Stat113), discovered because of their activation as transcription factors after interferon-induced tyrosine phosphorylation, shows several highly conserved regions, including the putative SH3 and SH2 domains.