Journal ArticleDOI
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
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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).Abstract:
Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), 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 then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.read more
Citations
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Journal ArticleDOI
A new protein containing an SH2 domain that inhibits JAK kinases
Takaho A. Endo,Masaaki Masuhara,Masahiro Yokouchi,Ritsu Suzuki,Hiroshi Sakamoto,Kaoru Mitsui,Akira Matsumoto,Shyu Tanimura,Motoaki Ohtsubo,Hiroyuki Misawa,Tadaaki Miyazaki,Nogueira Leonor,Tadatsugu Taniguchi,Takashi Fujita,Yuzuru Kanakura,S. Komiya,Akihiko Yoshimura +16 more
TL;DR: A new SH2-domain-containing protein is isolated, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain, and JAB and CIS appear to function as negative regulators in the JAK signalling pathway.
Book ChapterDOI
Regulation of interferon-gamma during innate and adaptive immune responses.
TL;DR: The epigenetic modifications and three-dimensional structure of the Ifng locus in naive CD4 T cells, and the modifications they undergo as these cells differentiate into effector T cells suggest a model whereby the chromatin architecture of Ifng is poised to facilitate either rapid opening or silencing during Th1 or Th2 differentiation, respectively.
Journal ArticleDOI
STATs: signal transducers and activators of transcription.
TL;DR: 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.
Journal ArticleDOI
Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice
Daniel H. Kaplan,Vijay Shankaran,Anand S. Dighe,Elisabeth Stockert,Michel Aguet,Lloyd J. Old,Robert D. Schreiber +6 more
TL;DR: It is demonstrated that endogenously produced interferon gamma (IFN-gamma) forms the basis of a tumor surveillance system that controls development of both chemically induced and spontaneously arising tumors in mice and is evidenced by the finding that certain types of human tumors become selectively unresponsive to IFN-Gamma.
Journal ArticleDOI
Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene.
Kazuya Shimoda,Jan van Deursent,Mark Y. Sangster,S R Sarawar,Richard T. Carson,Ralph A. Tripp,Charles C. Chu,Frederick W. Quelle,Tetsuya Nosaka,Dario A. A. Vignali,Peter C. Doherty,Gerard Grosveld,William E. Paul,James N. Ihle +13 more
TL;DR: Stat6-l- mice were deficient in IL-4-mediated functions including Th2 helper T-cell differentiation, expression of cell surface markers, and immunoglobulin class switching to IgE, indicating the lack of a non-redundant function in normal development.
References
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Journal ArticleDOI
Stimulation of 3T3 cells induces transcription of the c- fos proto-oncogene
TL;DR: Transcription of the c-fos proto-oncogene is greatly increased within minutes of administering purified growth factors to quiescent 3T3 cells, and this stimulation is the most rapid transcriptional response to peptide growth factors yet described, implying a role for c- fos in cell-cycle control.
Journal ArticleDOI
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TL;DR: Gel electrophoresis in studies of equilibrium binding, site distribution, and kinetics of protein-DNA interactions found that binding to the so-called third operator site (03) is 15-18 fold weaker than operator binding, and that the binding reactions with the first and third operators are uncoupled, implying that there is no communication between the sites.
Journal ArticleDOI
Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6
TL;DR: 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).
Journal ArticleDOI
SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins
TL;DR: Observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.
Journal ArticleDOI
A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system
Mark M. Garner,Arnold Revzin +1 more
TL;DR: It is demonstrated that even when pre-formed in the presence of CAP-cAMP, the polymerase-promoter open complex becomes unstable if CAP is then selectively removed, and this gel method is applied to the study of the E. coli lactose operon regulatory system.
Related Papers (5)
Transcriptional responses to polypeptide ligands: the JAK-STAT pathway.
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