Stat5a and Stat5b Proteins Have Essential and Nonessential, or Redundant, Roles in Cytokine Responses

@article{Teglund1998Stat5aAS,
  title={Stat5a and Stat5b Proteins Have Essential and Nonessential, or Redundant, Roles in Cytokine Responses},
  author={S. Teglund and C. Mckay and E. Schuetz and J. Deursen and D. Stravopodis and Demin Wang and Michael P. Brown and S. Bodner and G. Grosveld and J. Ihle},
  journal={Cell},
  year={1998},
  volume={93},
  pages={841-850}
}
A variety of cytokines mediate the activation of Janus protein tyrosine kinases (Jaks). The Jaks then phosphorylate cellular substrates, including members of the signal transducers and activators of transcription (Stat) family of transcription factors. Among the Stats, the two highly related proteins, Stat5a and Stat5b, are activated by a variety of cytokines. To assess the role of the Stat5 proteins, mutant mice were derived that have the genes deleted individually or together. The phenotypes… Expand
Signaling by STATs
TLDR
The physiological roles of STATs have been elucidated by analysis of mice rendered deficient in STAT genes and several auto-regulatory and signaling crosstalk mechanisms for regulating Jak–STAT signaling have been described. Expand
Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B.
TLDR
It is proposed that mice with mutations in various components of the JAK-STAT signaling pathway are living laboratories, which will provide insight into the versatility of signaling hardware and the adaptability of the software. Expand
Review Signaling by STATs
TLDR
The physiological roles of STATs have been elucidated by analysis of mice rendered deficient in STAT genes and several auto-regulatory and signaling crosstalk mechanisms for regulating Jak–STAT signaling have been described. Expand
STAT5 in Cancer and Immunity.
  • A. Rani, J. J. Murphy
  • Biology, Medicine
  • Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
  • 2016
TLDR
Signal transducers and activators of transcription 5 (STAT5a and STAT5b) are highly homologous proteins that are encoded by 2 separate genes and are activated by Janus-activated kinases downstream of cytokine receptors, which critically mediates the biological actions of members of the γ(c) family of cytokines in the immune system. Expand
Interleukins and STAT signaling.
TLDR
Under normal physiological conditions, initiation and attenuation of cytokine signals are tightly controlled via multiple cellular and molecular mechanisms, but Aberrant activation of cytokines signaling pathways is found under a variety of patho-physiological conditions including cancer and immune diseases. Expand
The role of Stat5a and Stat5b in signaling by IL-2 family cytokines
TLDR
The molecular mechanisms of how Stat5 is activated by IL-2 family cytokines from in vitro biochemical studies are summarized as well as the role that is played by Stat5 in each of the cytokine signaling pathways from in vivo gene-targeting analyses are summarized. Expand
CPAP is a novel stat5-interacting cofactor that augments stat5-mediated transcriptional activity.
TLDR
CPAP is identified as a novel coactivator of Stat5 proteins in the PRL pathways, and was found to augment Stat5-mediated transcription. Expand
Functional Roles of STAT Family Proteins: Lessons from Knockout Mice
TLDR
Analyses of tissue‐specific STAT3‐deficient mice indicate that STAT3 plays a crucial role in a variety of biological functions, including cell growth, suppression of apoptosis, and cell motility. Expand
Cytokines and STAT signaling.
TLDR
Signal transducers and activators of transcription (STATs) represent a family of conserved proteins, seven of which have been identified in mammals, and are now known to play a significant role in signal transduction for most cytokines. Expand
Biological Roles of the STAT Family in Cytokine Signaling
TLDR
Gene targeting of the SOCS family revealed that individual sacs proteins negatively regulate some cytokine-mediated signaling pathways, including the sacs family of proteins induced by activation of the JAK-STAT pathway. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 130 REFERENCES
STATs and gene regulation.
TLDR
The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins. Expand
Naturally occurring dominant negative variants of Stat5.
TLDR
The results demonstrate the natural existence of potentially dominantly suppressive variants of Stat5 and implicate the carboxyl domain of Stats in transcriptional regulation and functions related to dephosphorylation and Surprisingly, the tyrosine phosphorylation of the car Box5 forms is considerably more stable than that of the wild-type proteins. Expand
The Janus protein tyrosine kinase family and its role in cytokine signaling.
  • J. Ihle
  • Biology, Medicine
  • Advances in immunology
  • 1995
TLDR
It can be hypothesized that Jaks and Stats, if important for proliferation and differentiation, may be the targets for malignant transformation. Expand
STATs: Signal Transducers and Activators of Transcription
TLDR
Regarding biological functions, it can be anticipated that in the very near future the phenotypes of mice deficient in the remaining STATs will be described and will thus eliminate further speculation, and it would seem less likely as time goes on that additional family members will emerge. Expand
Targeted Disruption of the Stat1 Gene in Mice Reveals Unexpected Physiologic Specificity in the JAK–STAT Signaling Pathway
TLDR
These observations document that STAT1 plays an obligate and dedicated role in mediating IFN-dependent biologic responses and reveal an unexpected level of physiologic specificity for STAT1 action. Expand
Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells
TLDR
All IL-12 functions tested were disrupted, including the induction of IFN-γ, mitogenesis, enhancement of natural killer cytolytic function and Thl differentiation. Expand
Jak2 Is Essential for Signaling through a Variety of Cytokine Receptors
TLDR
Reconstitution experiments demonstrate that Jak2 is not required for the generation of lymphoid progenitors, their amplification, or functional differentiation, and plays a critical, nonredundant role in the function of a specific group of cytokines receptors. Expand
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.
TLDR
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). Expand
Interleukin 2 and erythropoietin activate STAT5/MGF via distinct pathways.
TLDR
It is demonstrated that interleukin 2 (IL‐2) as well as erythropoietin (EPO) stimulate STAT5 and induce tyrosine phosphorylation of STAT5, and IL‐4 induces a DNA binding factor which possesses similar, but distinct, DNA binding specificity from that ofSTAT5 and is immunologically different from STAT5. Expand
Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue.
TLDR
The increase of Stat5 expression during pregnancy coincides with the activation of the WAP gene, and the two RNAs are present in mammary tissue of immature virgin mice, and their levels increase up to day 16 of pregnancy, followed by a decline during lactation. Expand
...
1
2
3
4
5
...