Btk function in B cell development and response

Satterthwaite, Anne B.; Li, Zuomei; Witte, Owen N.

doi:10.1006/smim.1998.0123

Cited by 170 publications

(187 citation statements)

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“…Btk is preferentially expressed in B cells and is necessary for B-cell development (Kerner et al, 1995;Khan et al, 1995). Mutations in the Btk gene result in human X-linked agammaglobulinemia and murine X-linked immunodeficiency (Tsukada et al, 1993;Satterthwaite et al, 1998;Vihinen et al, 2000). Likewise, Itk is predominately expressed in T cells and is crucial in T-cell development and T-cell receptorinitiated signaling cascade (Bunnell et al, 2000;August et al, 2002;Miller and Berg, 2002).…”

Section: Introductionmentioning

confidence: 99%

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

et al. 2003

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Section: Introductionmentioning

confidence: 99%

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

et al. 2003

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“…Because the mechanism by which Btk signaling is modified varies among functional responses, an extension of these studies to other Btk-dependent pathways such as CD38, RP105, and IL-5 (reviewed in refs. [17][18][19] would likely demonstrate additional types of interactions.…”

Section: A Mammalian Sensitized Genetic System For the Identificatiomentioning

confidence: 99%

“…XLA and xid result from loss of function of Bruton's tyrosine kinase (Btk) (reviewed in refs. [16][17][18] and are characterized by blocks in B cell development at the pre-B stage in XLA and at the immature to mature transition in xid. The remaining B cells have impaired responses Abbreviations: Btk, Bruton's tyrosine kinase; Btk lo , Btk transgenic mice expressing 25% of endogenous Btk levels; TI-II, type II T cell independent antigen; xid, X-linked immunodeficiency; BCR, B cell antigen receptor; TNP, 2,4,6-trinitrophenyl; PI3K, phosphoinositide 3-kinase; PIP3, phosphatidylinositol 3,4,5-triphosphate; FITC, fluorescein isothiocyanate; PE, phycoerythrin; SHIP, SH2-containing inositol phosphatase; PTEN, phosphatase and tensin homolog; PKC␤, protein kinase C␤.…”

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confidence: 99%

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confidence: 99%

“…[17][18][19]. Conflicting results regarding the nature of the interaction between Btk and several other signaling molecules have been reported.…”

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A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase

Satterthwaite

Willis

Kanchanastit

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Modifier screens have been powerful genetic tools to define signaling pathways in lower organisms. The identification of modifier loci in mice has begun to allow a similar dissection of mammalian signaling pathways. Transgenic mice (Btk lo ) expressing 25% of endogenous levels of Bruton's tyrosine kinase (Btk) have B cell functional responses between those of wild-type and Btk ؊/؊ mice. We asked whether reduced dosage or complete deficiency of genes previously implicated as Btk regulators would modify the Btk lo phenotype. We used two independent assays of Btk-dependent B cell function. Proliferative response to B cell antigen receptor cross-linking in vitro was chosen as an example of a relatively simple, well-defined signaling system. In vivo response to type II T-independent antigens (TI-II) measures complex interactions among multiple cell types over time and may identify additional Btk pathways. All modifiers identified differentially affected these two assays, indicating that Btk mediates these processes via distinct mechanisms. Loss of Lyn, PTEN (phosphatase and tensin homolog), or SH2-containing inositol phosphatase suppressed the Btk lo phenotype in vitro but not in vivo, whereas CD19 and the p85␣ form of phosphoinositide 3-kinase behaved as Btk lo enhancers in vivo but not in vitro. Effects of Lyn, PTEN, or p85␣ haploinsufficiency were observed. Haploinsufficiency or complete deficiency of protein kinase C ␤, Fyn, CD22, G␣q, or G␣11 had no detectable effect on the function of Btk lo B cells. A transgenic system creating a reduction in dosage of Btk can therefore be used to identify modifier loci that affect B cell responses and quantitatively rank their contribution to Btk-mediated processes.In vivo genetic analysis is a powerful approach to define the relative contribution of signaling interactions to physiological processes. Small genomes, ease of mutagenesis, and rapid generation time have made Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae the major models for genetic dissection of eukaryotic signaling pathways. Although there are some examples of large-scale genetic screens in mice (1-3), time, space, and financial resources generally limit mammalian genetic studies to targeted mutations in known genes or the characterization of naturally occurring mutations.In a commonly used type of genetic screen, organisms carrying a defined mutation affecting the process of interest are further mutagenized and screened for second site mutations, or modifiers, that enhance (increase) or suppress (reduce) the severity of the parental phenotype (4, 5). The initial mutation often renders the system responsive to subtle changes in modifiers that would not be penetrant on an otherwise wild-type background. This sensitivity often permits a dominant screen, decreasing the time and resources required to identify new mutations.Complete deficiency of many signaling molecules results in loss of the cell type of interest or pleiotropic or lethal phenotypes, making the effects of additional m...

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BTK mediated apoptosis, a possible mechanism for failure to generate high titer retroviral producer clones

et al. 2000

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Btk function in B cell development and response

Cited by 170 publications

References 0 publications

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase

BTK mediated apoptosis, a possible mechanism for failure to generate high titer retroviral producer clones

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