Signalling in B cells

Alés-Martínez, JoséE.; Cuende, Eduardo; Martı́nez-A, Carlos; Parkhouse, R. M. E.; Pezzi, Luis; Scott, David W.

doi:10.1016/0167-5699(91)90054-w

Cited by 48 publications

(15 citation statements)

References 41 publications

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“…Aggregation of these receptors initiates a rapid increase in tyrosine phosphorylation of subunits of the receptors and of several other cellular proteins (35,36,(42)(43)(44)(45)(46). Src family tyrosine kinases are thought to be important for phosphorylating the receptor subunits which then recruits Syk/ZAP70 family tyrosine kinases and leads to the activation of downstream signals.…”

Section: Identification Of a Cell Line Expressing Low Levels Of Fak-mentioning

confidence: 99%

Reconstitution of High Affinity IgE Receptor-mediated Secretion By Transfecting Protein Tyrosine Kinase pp125FAK

Hamawy

Swieter

Mergenhagen

et al. 1997

Journal of Biological Chemistry

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To study the role of the focal adhesion tyrosine kinase (FAK) in receptor-mediated secretion, we transfected FAK cDNA into a variant (3B6) of the RBL-2H3 mast cell line. This 3B6 cell line expressed low levels of FAK and was defective in high affinity IgE receptor (Fc⑀RI) but not Ca 2؉ ionophore-mediated secretion. Fc⑀RI-mediated secretion was reconstituted after transfection of wildtype FAK. Histamine release was also enhanced by the stable expression of two mutants of FAK: a kinase-inactive form in which the ATP binding site Lys-454 was replaced by Arg or a mutant in which the autophosphorylation site Tyr-397 was replaced by Phe. Therefore, the catalytic activity and the autophosphorylation site of FAK are not essential for secretion. Fc⑀RI aggregation increased the tyrosine phosphorylation of both mutants of FAK to the same extent as wild-type FAK. Therefore, tyrosine kinases activated by Fc⑀RI aggregation are phosphorylating FAK and some of these phosphorylation sites are other than Tyr-397. These results strongly suggest that FAK plays a role in Fc⑀RI-induced secretion by functioning as an adapter or linker molecule.The focal adhesion kinase (FAK) 1 is a widely expressed tyrosine kinase that localizes with integrins and several proteins to intracellular sites where cells are in contact with the extracellular matrix (1, 2). FAK also becomes tyrosine-phosphorylated in response to the activation of various receptors including the high affinity IgE receptor (Fc⑀RI) and Ag receptors on T-cells (1-4). FAK is essential for development as the inactivation through homologous recombination of the FAK gene results in early embryonal mesodermal defects, retarded growth, and prenatal death (5).Previously, we reported that the aggregation of Fc⑀RI results in tyrosine phosphorylation of FAK in rat basophilic leukemia RBL-2H3 cells, a mast cell line that has been extensively used to study Fc⑀RI-mediated secretion (3). This receptor-induced phosphorylation of FAK and secretion from these cells are enhanced by adherence of the cells to fibronectin (3, 6). Furthermore, a monoclonal antibody to a ganglioside present on the RBL-2H3 cells induces many of the same intracellular reactions initiated by Fc⑀RI aggregation but fails to result in tyrosine phosphorylation of FAK and does not result in secretion (7). These experiments suggest that FAK may play a role in secretion from mast cells and basophils.To further define the role of FAK in secretion, we transfected FAK cDNA into a variant of the RBL-2H3 mast cell line that expressed low levels of this kinase and had decreased Fc⑀RI, but not Ca 2ϩ ionophore-mediated secretion. Fc⑀RI-induced histamine release was reconstituted in the cell lines that expressed increased levels of FAK. These studies demonstrate a function for FAK in Fc⑀RI-mediated secretion.

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Section: Identification Of a Cell Line Expressing Low Levels Of Fak-mentioning

confidence: 99%

Reconstitution of High Affinity IgE Receptor-mediated Secretion By Transfecting Protein Tyrosine Kinase pp125FAK

Hamawy

Swieter

Mergenhagen

et al. 1997

Journal of Biological Chemistry

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“…In general, crosslinking of the receptor complex of resting B cells by antigens or antibodies to the immunoglobulins activates B cells to enter the G1 phase of the cell cycle, in which they become susceptible to proliferative signals provided by helper T cells. These responses are preceded by phosphatidylinositol turnover, activation of phospholipase C, and Ca2+ mobilization, which are apparently dependent on the functions of a GTP-binding protein(s), protein-tyrosine kinase(s), and protein-tyrosine-phosphatase(s) (1,2). The tyrosine phosphorylation of proteins after mlg crosslinking is thought to be an initial intracellular signaling event.…”

mentioning

confidence: 99%

“…Membrane-bound immunoglobulin (mIg) forms an antigen receptor complex on the plasma membrane of B cells with at least two transmembrane proteins, MB-1 and B29 (1)(2)(3). In general, crosslinking of the receptor complex of resting B cells by antigens or antibodies to the immunoglobulins activates B cells to enter the G1 phase of the cell cycle, in which they become susceptible to proliferative signals provided by helper T cells.…”

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confidence: 99%

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Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.

Yamanashi

Okada

Semba

et al. 1993

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

145

135

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Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen receptors, causes proliferation and differentiation of B cells or inhibition of their growth.The receptor-mediated signaling involves tyrosine phosphorylation of cellular proteins and rapid activation of Src-like kinases. The amino acid sequences of five proteolytic peptides of p75, a major substrate of protein-tyrosine kinase(s) in the signaling, showed that p75 is the human HS1 gene product. The HS1 gene is expressed specifically in hematopoietic cells and encodes p75HSl, which carries both helix-turhelix and Src homology 3 motifs. p75HSl showed rapid tyrosine phosphorylation and association with a Src-like kinase, Lyn, after crosslinking of membrane-bound IgM. Thus, p75HS1 may be an important substrate of Lyn and possibly other protein-tyrosine kinases upon B-cell antigen receptor-mediated signaling.Membrane-bound immunoglobulin (mIg) forms an antigen receptor complex on the plasma membrane of B cells with at least two transmembrane proteins, MB-1 and B29 (1-3). In general, crosslinking of the receptor complex of resting B cells by antigens or antibodies to the immunoglobulins activates B cells to enter the G1 phase of the cell cycle, in which they become susceptible to proliferative signals provided by helper T cells. These responses are preceded by phosphatidylinositol turnover, activation of phospholipase C, and Ca2+ mobilization, which are apparently dependent on the functions of a GTP-binding protein(s), protein-tyrosine kinase(s), and protein-tyrosine-phosphatase(s) (1, 2). The tyrosine phosphorylation of proteins after mlg crosslinking is thought to be an initial intracellular signaling event. As mlg, MB-1, and B29 carry no catalytic domain, the receptor must regulate protein-tyrosine kinase(s) as an intracytoplasmic signal transducer(s) (1-3).Src-like kinases are intracytoplasmic protein-tyrosine kinases of 55-60 kDa that are thought to be localized on the inner part of the plasma membrane via myristic acid (4, 5).

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“…A mature B-cell is activated when it encounters Ag that expresses epitopes that are recognized by surface Ig. The activation process may involve the direct crosslinking of surface Ig in a process called T-independent activation, so named because the B-cells are directly activated without additional signals delivered by immune T-cells [60]. T-independent Ags are highly repetitious structures and are generally components of bacterial cell walls (e.g.…”

Section: B-cell Activationmentioning

confidence: 99%

Role of T- and B-lymphocytes in pulmonary host defences

Moore¹,

Moore²,

Toews³

2001

European Respiratory Journal

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Pulmonary infectious diseases cause significant morbidity and mortality in both industrialized and developing countries.Adaptive immune responses are required to defend the lung against pathogens that survive in normal macrophages and extracellular organisms that evade phagocytosis. Microbes initiate both innate immune responses and specific adaptive immune responses.Innate immune response molecules regulate T-lymphocyte differentiation. Activated T-lymphocytes provide cytokines, which activate macrophages and lytic signals that lyse infected antigen-presenting cells.Antibodies produced by plasma cells facilitate microbial clearance through diverse effector mechanisms including opsonization, complement fixation and antibodydependent cytotoxicity. Lymphocytes determine the specificity of the immune response and orchestrate effector limbs of the immune response.

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Signalling in B cells

Cited by 48 publications

References 41 publications

Reconstitution of High Affinity IgE Receptor-mediated Secretion By Transfecting Protein Tyrosine Kinase pp125FAK

Reconstitution of High Affinity IgE Receptor-mediated Secretion By Transfecting Protein Tyrosine Kinase pp125FAK

Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.

Role of T- and B-lymphocytes in pulmonary host defences

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