Disruption of the Jak1 Gene Demonstrates Obligatory and Nonredundant Roles of the Jaks in Cytokine-Induced Biologic Responses

  title={Disruption of the Jak1 Gene Demonstrates Obligatory and Nonredundant Roles of the Jaks in Cytokine-Induced Biologic Responses},
  author={Scott J. Rodig and Marco Antonio Meraz and J.Michael White and Patricia A. Lampe and Joan K. Riley and Cora D. Arthur and Kathleen L. King and Kathleen C.F. Sheehan and Li Yin and Diane Pennica and Eugene M. Johnson and Robert D. Schreiber},

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Jak2 Is Essential for Signaling through a Variety of Cytokine Receptors

The Janus kinases (Jaks)

The essential, nonredundant functions of Jaks in cytokine signaling have been established, and deficiency of Jak3 is the basis of human autosomal recessive severe combined immunodeficiency (SCID); accordingly, a selective Jak3 inhibitor has been developed, forming a new class of immunosuppressive drugs.

Characterization of JAK1 Pseudokinase Domain in Cytokine Signaling

Mechanistic understanding is brought about about the function of JAK1 in different receptor complexes that likely have relevance for the design of specific JAK modulators.

Negative regulation of Janus kinases

The basis of these and other mechanisms of negative regulation of Jak activity, including the suppression of jak expression levels caused by tumor- or pathogen-derived agents, the complex interactions of JAKs with phosphatases, and the redox regulation ofJAK catalytic activity, is the focus of this review.

Therapeutic targeting of Janus kinases

A great deal is learned about the feasibility and effectiveness of targeting Janus kinases, and it appears likely that this will be a fruitful strategy in a variety of settings.

Function of JAKs and STATs in Lymphocytes: Bench to Bedside

The following chapter will discuss the key role played by JAKs and STATs in the lymphocytes, with special emphasis on helper T cells, which are not only critical mediators of pathogenic inflammation, but also an outstanding model system for investigating JAK/STAT biology.

Generation of Janus kinase 1 (JAK1) conditional knockout mice

Examination of fibroblasts from conditional knockout embryos and their littermate wildtype controls expressing JAK1 showed that lack of this Janus kinase resulted in an impaired tyrosine phosphorylation and activation of the downstream Signal Transducers and Activators of Transcription (STATs) 1, 3, and 6.



Jak2 Is Essential for Signaling through a Variety of Cytokine Receptors

Defective Lymphoid Development in Mice Lacking Jak3

Jak3 plays a critical role in γc signaling and lymphoid development in thymocytes and severe B cell and T cell lymphopenia similar to severe combined immunodeficiency disease (SCID).

Defects in B Lymphocyte Maturation and T Lymphocyte Activation in Mice Lacking Jak3

Data demonstrate that Jak3 is critical for the progression of B cell development in the bone marrow and for the functional competence of mature T cells.

Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.

Unlike other cytokine receptors studied to date, the receptors for the CNTF cytokine family utilize all known members of the Jak-Tyk family, but induce distinct patterns of Jak- Tyk phosphorylation in different cell lines.

Interleukin-6 family of cytokines and gp130.

It is shown that IL-6, together with IL-3, induces the expansion of murine hematopoietic progenitor cells and to be responsible for stimulating resting cells to enter the Cl-phase, a fact that may explain the redundant activities of IL- 6 and LIF.

Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders.

  • K. YoshidaT. Taga T. Kishimoto
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
Results indicate that gp130 plays a crucial role in myocardial development and hematopoiesis during embryogenesis and some gp130-/- embryos show anemia due to impaired development of erythroid lineage cells.