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BTK
Bruton’s Tyrosine Kinase

BTK
Bruton’s Tyrosine Kinase

Overview

Bruton’s tyrosine kinase (BTK) is a nonreceptor kinase that is a critical mediator in oncogenic signaling that spurs the proliferation and survival of leukemic cells in many B-cell malignancies. BTK was originally shown to be mutated in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and has been shown to have an essential role at various stages of B-lymphocyte development and the function of mature B cells.1 BTK is essential in regulating signaling through the B-cell receptor in response to antigen.2,3

Following antigen recognition and binding by the surface B-cell receptor, BTK is recruited to the cell membrane where it becomes activated by a series of phosphorylations.3 Following activation, BTK initiates a signaling cascade critical to the production of antibodies, proinflammatory cytokines and chemokines, as well as influencing antigen presentation on B cells.1

B cells, in addition to being a source of autoantibodies, also play a critical role in autoimmunity through antibody-independent mechanisms, including the action of B cells as antigen-presenting cells and as sources of proinflammatory cytokines.4

BTK is also expressed to high levels in myeloid lineages such as macrophages and granulocytes and regulates the signaling pathways leading to expression of proinflammatory cytokines, induced in autoimmune disorders through the binding of immune complexes to the Fcγ receptors.2

Adapted from Priority Review for Potent Novel Therapy for CLL

Adapted from Priority Review for Potent Novel Therapy for Chronic Lymphocytic Leukemia (CLL). http://blogs.shu.edu/cancer/2016/01/20/priority-review-for-potent-novel-therapy- for-chronic-lymphocytic-leukemia-cll/

BTK Pathway

References

  1. Pal Singh S, Dammeijer F, Hendriks RW. Role of Bruton's tyrosine kinase in B cells and malignancies. Mol Cancer. 2018;17(1):r57.
  2. Chu AD, Chang BY. B-cell kinase inhibitors in rheumatoid arthritis. OA Arthritis. 2013;1(2):17.
  3. Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013;6:59.
  4. Burmester GR, Feist E, Dorner T. Emerging cell and cytokine targets in rheumatoid arthritis. Nature. 2014;10:77-88.