Structure and function of Tec family kinase Itk

Qi, Qian; Kannan, A.; August, Avery

doi:10.1515/bmc.2011.020

Cited by 2 publications

(2 citation statements)

References 86 publications

(150 reference statements)

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“…Moreover, Btk is central in control of the Toll-like receptor (TLR)-induced IL-10 expression by B cells, and is an active part of the NLRP3 inflammasome, a multimeric protein complex that triggers the release of proinflammatory cytokines, such as IL-1β and IL-18, in many inflammatory conditions, including Alzheimer’s disease, diabetes, and infections ( 55 ), and lack of Btk can lead to a compromised BCR-induced proliferation and survival. Finally, Itk is responsible for T cell development, differentiation and signaling ( 56 ).…”

Section: The Role Of Syk Btk and Itk In The Development Of Cgvhdmentioning

confidence: 99%

New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions

et al. 2020

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Chronic graft-versus-host disease (cGvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation that affects various organs leading to a reduced quality of life. The condition often requires enduring immunosuppressive therapy, which can also lead to the development of severe side effects. Several approaches including small molecule inhibitors, antibodies, cytokines, and cellular therapies are now being developed for the treatment of cGvHD, and some of these therapies have been or are currently tested in clinical trials. In this review, we discuss these emerging therapies with particular emphasis on tyrosine kinase inhibitors (TKIs). TKIs are a class of compounds that inhibits tyrosine kinases, thereby preventing the dissemination of growth signals and activation of key cellular proteins that are involved in cell growth and division. Because they have been shown to inhibit key kinases in both B cells and T cells that are involved in the pathophysiology of cGvHD, TKIs present new promising therapeutic approaches. Ibrutinib, a Bruton tyrosine kinase (Btk) inhibitor, has recently been approved by the Food and Drug Administration (FDA) in the United States for the treatment of adult patients with cGvHD after failure of first-line of systemic therapy. Also, Janus Associated Kinases (JAK1 and JAK2) inhibitors, such as itacitinib (JAK1) and ruxolitinib (JAK1 and 2), are promising in the treatment of cGvHD. Herein, we present the current status and future directions of the use of these new drugs with particular spotlight on their targeting of specific intracellular signal transduction cascades important for cGvHD, in order to shed some light on their possible mode of actions.

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Section: The Role Of Syk Btk and Itk In The Development Of Cgvhdmentioning

confidence: 99%

New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions

et al. 2020

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“…ITK and BTK are members of the Tec family of kinases, which are primarily expressed in cells of hematopoietic lineage [ 51 ]. Based upon the following correlations: (1) Cx43-mediated signaling occurs at the immunological synapse (and non-synaptical regions) [ 52 , 53 ], (2) BTK and ITK are activated via the B-cell and T-cell receptors at the immunological synapse [ 54 , 55 ], (3) down-stream signaling cascades upon B-cell and T-cell receptor activation do not directly involve activation of c-Src [ 54 , 56 ], and (4) phosphorylation of Cx43 residues Y247 and Y265 is necessary for B-cell spreading in response to B-cell receptor signaling [ 57 ], we tested whether the activation of BTK and ITK regulate Cx43 in a similar manner as Pyk2, Tyk2, and Src.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Cx43 Gap Junction Intercellular Communication by Bruton’s Tyrosine Kinase and Interleukin-2-Inducible T-Cell Kinase

Basu

Trease

et al. 2023

Biomolecules

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T and B cell receptor signaling involves the activation of Akt, MAPKs, and PKC as well as an increase in intracellular Ca2+ and calmodulin activation. While these coordinate the rapid turnover of gap junctions, also implicated in this process is Src, which is not activated as part of T and B cell receptor signaling. An in vitro kinase screen identified that Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK) phosphorylate Cx43. Mass spectroscopy revealed that BTK and ITK phosphorylate Cx43 residues Y247, Y265, and Y313, which are identical to the residues phosphorylated by Src. Overexpression of BTK or ITK in the HEK-293T cells led to increased Cx43 tyrosine phosphorylation as well as decreased gap junction intercellular communication (GJIC) and Cx43 membrane localization. In the lymphocytes, activation of the B cell receptor (Daudi cells) or T cell receptor (Jurkat cells) increased the BTK and ITK activity, respectively. While this led to increased tyrosine phosphorylation of Cx43 and decreased GJIC, the cellular localization of Cx43 changed little. We have previously identified that Pyk2 and Tyk2 also phosphorylate Cx43 at residues Y247, Y265, and Y313 with a similar cellular fate to that of Src. With phosphorylation critical to Cx43 assembly and turnover, and kinase expression varying between different cell types, there would be a need for different kinases to achieve the same regulation of Cx43. The work presented herein suggests that in the immune system, ITK and BTK have the capacity for the tyrosine phosphorylation of Cx43 to alter the gap junction function in a similar manner as Pyk2, Tyk2, and Src.

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Structure and function of Tec family kinase Itk

Cited by 2 publications

References 86 publications

New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions

New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions

Regulation of Cx43 Gap Junction Intercellular Communication by Bruton’s Tyrosine Kinase and Interleukin-2-Inducible T-Cell Kinase

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