The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases

Vetrie, David; Vořechovský, Igor; Sideras, Paschalis; Holland, Jill; Davies, Adelina A.; Flinter, Frances; Hammarström, Lennart; Kinnon, Christine; Levinsky, Roland J.; Bobrow, Martin

doi:10.1038/361226a0

Cited by 1,375 publications

(884 citation statements)

References 54 publications

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“…Because many members of this family have been shown to be activated in response to growth and differentiation stimuli in hematopoietic tissues, they are presumed to function in vivo as important signaling mediators 17; indeed, mutations in Btk cause agammaglobulinemia in humans 18 25.…”

mentioning

confidence: 99%

Txk, a Nonreceptor Tyrosine Kinase of the Tec Family, Is Expressed in T Helper Type 1 Cells and Regulates Interferon γ Production in Human T Lymphocytes

Kashiwakura

Suzuki

Nagafuchi

et al. 1999

The Journal of Experimental Medicine

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Differentiation of human T cells into T helper (Th)1 and Th2 cells is vital for the development of cell-mediated and humoral immunity, respectively. However, the precise mechanism responsible for the Th1 cell differentiation is not fully clarified. We have studied the expression and function of Txk, a member of the Tec family of nonreceptor tyrosine kinases. We found that Txk expression is restricted to Th1/Th0 cells with IFN-γ producing potential. Txk transfection of Jurkat T cells resulted in a several-fold increase of IFN-γ mRNA expression and protein production; interleukin (IL)-2 and IL-4 production were unaffected. Antisense oligodeoxynucleotide of Txk specifically inhibited IFN-γ production of normal peripheral blood lymphocytes, antigen-specific Th1 clones, and Th0 clones; IL-2 and IL-4 production by the T cells was unaffected. Txk cotransfection led to the enhanced luciferase activity of plasmid (p)IFN-γ promoter/enhancer (pIFN-γ[-538])-luciferase–transfected Jurkat cells upon mitogen activation. Txk transfection did not affect IL-2 and IL-4 promoter activities. Thus, Txk specifically upregulates IFN-γ gene transcription. In fact, Txk translocated from cytoplasm into nuclei upon activation and transfection with a mutant Txk expression plasmid that lacked a nuclear localization signal sequence did not enhance IFN-γ production by the cells, indicating that nuclear localization of Txk is obligatory for the enhanced IFN-γ production. In addition, IL-12 treatment of peripheral blood CD4+ T cells enhanced the Txk expression, whereas IL-4 treatment completely inhibited it. These results indicate that Txk expression is intimately associated with development of Th1/Th0 cells and is significantly involved in the IFN-γ production by the cells through Th1 cell–specific positive transcriptional regulation of the IFN-γ gene.

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confidence: 99%

Txk, a Nonreceptor Tyrosine Kinase of the Tec Family, Is Expressed in T Helper Type 1 Cells and Regulates Interferon γ Production in Human T Lymphocytes

Kashiwakura

Suzuki

Nagafuchi

et al. 1999

The Journal of Experimental Medicine

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“…Thus, mutations in the BTK gene in humans cause a severe B cell deficiency X‐linked, agammaglobulinemia (XLA) 36, 37. In affected individuals, a defect in B cell maturation and function leads to the profound reduction of serum immunoglobulins and increased susceptibility to infections 38.…”

Section: Tec Family Kinasesmentioning

confidence: 99%

Targets for Ibrutinib Beyond B Cell Malignancies

et al. 2015

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Ibrutinib (Imbruvica™) is an irreversible, potent inhibitor of Bruton's tyrosine kinase (BTK). Over the last few years, ibrutinib has developed from a promising drug candidate to being approved by FDA for the treatment of three B cell malignancies, a truly remarkable feat. Few, if any medicines are monospecific and ibrutinib is no exception; already during ibrutinib's initial characterization, it was found that it could bind also to other kinases. In this review, we discuss the implications of such interactions, which go beyond the selective effect on BTK in B cell malignancies. In certain cases, the outcome of ibrutinib treatment likely results from the combined inhibition of BTK and other kinases, causing additive or synergistic, effects. Conversely, there are also examples when the clinical outcome seems unrelated to inhibition of BTK. Thus, more specifically, adverse effects such as enhanced bleeding or arrhythmias could potentially be explained by different interactions. We also predict that during long‐term treatment bone homoeostasis might be affected due to the inhibition of osteoclasts. Moreover, the binding of ibrutinib to molecular targets other than BTK or effects on cells other than B cell‐derived malignancies could be beneficial and result in new indications for clinical applications.

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“…In these cases the panel reckoned appropriate to proceed to further more targeted analyses (genomic DNA mutation study for Shwachman-Diamond, mitochondrial DNA analysis for Pearson's syndrome, erythrocyte ADA and mutation search for Blackfan-Diamond syndrome) [18][19][20][21] aiming to make a firm diagnosis of these diseases (Table VII) In the case of early, severe and recurrent infections associated to decreased Ig serum levels, increased CRP and positive markers LGL syndrome Associated to hypersplenism (AEanemia, AEthrombocytopenia) Associated to sequestration in infectious foci of infections, overall suggesting an immunodeficiency, peripheral blood immunophenotype, response to vaccines including polysaccharide antigens, lymphocyte proliferation to mytogens are indicated before referring the patient to an Immunodeficiency Reference Center where study of mutations of genes involved in neutropenia associated with immunodeficiency can be addressed [22][23][24][25][26][27][28][29][30][31][32][33][34] (Table VII) …”

Section: Diagnostic Itinerarymentioning

confidence: 99%

Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica)

Fioredda

Calvillo

Bonanomi

et al. 2011

Pediatric Blood & Cancer

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Congenital and acquired neutropenia are rare disorders whose frequency in pediatric age may be underestimated due to remarkable differences in definition or misdiagnosed because of the lack of common practice guidelines. Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document which includes a classification of neutropenia and a comprehensive guideline on diagnosis of neutropenia. Pediatr Blood Cancer 2011;57:10–17. © 2011 Wiley‐Liss, Inc.

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The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases

Cited by 1,375 publications

References 54 publications

Txk, a Nonreceptor Tyrosine Kinase of the Tec Family, Is Expressed in T Helper Type 1 Cells and Regulates Interferon γ Production in Human T Lymphocytes

Txk, a Nonreceptor Tyrosine Kinase of the Tec Family, Is Expressed in T Helper Type 1 Cells and Regulates Interferon γ Production in Human T Lymphocytes

Targets for Ibrutinib Beyond B Cell Malignancies

Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica)

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