CCL

Összesen 10 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM054305
035-os BibID:PMID: 18243342
Első szerző:Hancz Anikó
Cím:Integration of signals mediated by B-cell receptor, B-cell activating factor of the tumor necrosis factor family (BAFF) and Fas (CD95) / Anikó Hancz, Zoltán Hérincs, Zsuzsa Neer, Gabriella Sármay, Gábor Koncz
Dátum:2008
ISSN:0165-2478
Megjegyzések:The survival of the mature resting B cells depends on signaling from B cell receptor (BCR), and a plethora of positive and negative regulators, that maintain cellular homeostasis and ultimately determine cell's fate, i.e., survival or programmed death (apoptosis). Among these regulators we have investigated the B cell activating factor belonging to tumor necrosis factor family (BAFF) and the prototypic death receptor Fas/CD95 mediated signals. We have shown that BAFF inhibits Fas-mediated cell death, however, the BCR-driven survival signals were not strengthened by BAFF. Therefore, we propose that BAFF may function independently of the antigen specificity of BCR, thus may enhance the risk of autoimmune diseases by promoting the survival of bystander B cells in the germinal center.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
B-cell
BAFF
Fas
apoptosis
selection
signaling
Megjelenés:Immunology Letters. - 116 : 2 (2008), p. 211-217. -
További szerzők:Hérincs Zoltán Neer Zsuzsa Sármay Gabriella Koncz Gábor (1970-) (biológus, immunológus)
Pályázati támogatás:D48469
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

2.

001-es BibID:BIBFORM041843
Első szerző:Hancz Anikó
Cím:TLR9-mediated signals rescue B-cells from Fas-induced apoptosis via inactivation of caspases / Anikó Hancz, Gábor Koncz, Dániel Szili, Gabriella Sármay
Dátum:2012
ISSN:0165-2478
Megjegyzések:The death receptor, CD95/Fas, serves to eliminate potentially dangerous, self-reactive B cells. Engagement of B-cell receptors (BCR) on mature B-cells mediates the escape from cell death resulting in the activation and expansion of antigen specific clones. In addition to the antigen receptors, the receptors of B-cell activating factor belong to the tumor necrosis factor (TNF) family (BAFFR); moreover, the pattern recognition receptor, TLR9 may also deliver survival signals inhibiting Fas-mediated death of B-cells. Our aim was to compare the mechanism of BCR-induced and the BAFFR- or TLR9-stimulated rescue of B-cells from CD95/Fas-mediated apoptosis. We have found that BAFFR and TLR9 collaborate with BCR to protect B-cells from Fas-induced elimination and the rescue is independent of protein synthesis. The results revealed that the TLR9- and BCR-triggered rescue signals are transmitted through partially overlapping pathways; the protein kinase C (PKC) and the abl kinase induced phosphorylation may inactivate caspases in both CpG and anti-IgG stimulated cells. However, PI3-K activation is crucial upon the BCR driven anti-apoptotic effect, while p38 MAPK-mediated inactivation of caspases seems to play essential role in TLR9-mediated protection against Fas-induced programmed cell death.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Apoptosis
BAFF
B-cells
Fas
TLR9
Megjelenés:Immunology Letters. - 143 : 1 (2012), p. 77-84. -
További szerzők:Koncz Gábor (1970-) (biológus, immunológus) Szili Dániel Sármay Gabriella
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

3.

001-es BibID:BIBFORM072879
Első szerző:Hancz Dóra
Cím:Flagellin increases death receptor-mediated cell death in a RIP1-dependent manner / Hancz Dora, Szabo Aniko, Molnar Tamás, Varga Zsofia, Hancz Aniko, Gregus Andrea, Hueber Anne-Odile, Rajnavolgyi Eva, Koncz Gabor
Dátum:2018
ISSN:0165-2478
Megjegyzések:Efficient adjuvants have the potential to trigger both innate and adaptive immune responses simultaneously. Flagellin is a unique pathogen-derived protein, which is recognized by pattern recognition receptors (PRRs) as well as by B-cell and T cell receptors thus providing an important link between innate and adaptive immunity. The aforementioned properties define flagellin as an optimal adjuvant. The induction of immunogenic cell death could be an additional expectation for adjuvants in the context of cancer immunotherapy due to their ability to activate dendritic cells (DC) to present tumor antigens through the engulfment of dying cells. The immunostimulatory potential of flagellin in the course of DC and lymphocyte activation is well documented, however the exact mechanism is not fully explored. Based on this limitation we sought to investigate the potential modulatory effects of flagellin on various cell death processes knowing that it plays detrimental roles in regulating the final outcome of various types of immune responses. Here we provide evidence that the pre-treatment of Jurkat T-cells with recombinant flagellin is able to increase the degree of cell death provoked by FasL or TNF-?, and concomitantly increases the cytotoxic potential of phytohemagglutinin activated T-lymphocytes in a TLR5 dependent way. In contrast to these flagellin-mediated effects on the death receptor-induced signaling events, the mitochondrial apoptotic pathway remained unaffected. Furthermore, the cell culture supernatant of wild type Salmonella enteritidis bacteria, but not their flagellin deficient variant, was able to enhance the Fas-induced cell death process. To define the molecular mechanisms of flagellin-mediated elevated levels of cell death we were able to detect the upregulation of RIP1-dependent signaling events. These findings demonstrate that the cooperative actions of pattern recognition and different death receptors are able to initiate the cell death process with the mobilization of RIP-dependent cell death modalities. This finding highlights the capability of flagellin to act as a potential adjuvant which is relevant for tumor immunotherapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adjuvant
Apoptosis
Necroptosis
PAMP
T cell
TLR
Megjelenés:Immunology Letters. - 193 (2018), p. 42-50. -
További szerzők:Szabó Anikó Molnár Tamás (1989-) (molekuláris biológus) Varga Zsófia (1992-) (molekuláris biológus) Hancz Anikó Gregus Andrea (1980-) (biológus) Hueber, Anne-Odile Rajnavölgyi Éva (1950-) (immunológus) Koncz Gábor (1970-) (biológus, immunológus)
Pályázati támogatás:OTKA-114423
OTKA
GINOP-2.3.2-15-2016-00050
GINOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

4.

001-es BibID:BIBFORM054308
035-os BibID:PMID: 12008033
Első szerző:Koncz Gábor (biológus, immunológus)
Cím:BCR mediated signal transduction in immature and mature B cells / Gábor Koncz, Csaba Bodor, Dorottya Kövesdi, Róbert Gáti, Gabriella Sármay
Dátum:2002
ISSN:0165-2478
Megjegyzések:Ligation of B cell receptors (BCR) on immature B cells may induce apoptosis, while in mature B cells it stimulates cell activation and growth. The signaling pathway regulating the differential functional response, death or survival of the B cell is not fully characterized. We have tested the intracellular signaling requirement of these processes using B cells isolated from the spleen of irradiated auto-reconstituted (transitional immature B cells) and untreated mice (mature B cells), respectively. We compared the BCR induced intracellular [Ca(2+)] transient, protein tyrosine phosphorylation and ERK phosphorylation, furthermore, the activation of Elk-1 and CREB transcription factors. The BCR induced rise of intracellular [Ca(2+)] did not significantly differ in the two populations, only a slight difference in the late phase of the response was observed. Immature B cells responded with a maximum tyrosine phosphorylation to a five times lower dose of anti-IgM compared to the mature population. Most importantly, we have found a significant difference in the tyrosine phosphorylation of the Gab family adaptor proteins, Gab1/2. In contrast to mature B cells, crosslinking of BCR on immature B cells did not induce tyrosine phosphorylation of Gab2, thus the Gab2-organized signal amplification complex could not be produced. Furthermore, we detected a significant difference in the kinetics of BCR induced ERK, Elk-1 and CREB phosphorylation. In immature B cells, ERK was transiently phosphorylated, ceasing after 120 min, while in mature cells, ERK phosphorylation was sustained. Elk-1 and CREB activation was also transient in immature B cells, followed the kinetics of ERK phosphorylation. The lack of sustained Erk1/2 activation suppresses the transcription factors necessary for the proliferation signal. Since ERK is regulated by the phosphorylated Gab1/2, these data demonstrate that BCR triggered phosphorylation and signal amplification of Gab1/2 is a critical step in a life or death decision of B cells.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Immunology Letters. - 82 : 1-2 (2002), p. 41-49. -
További szerzők:Bodor Csaba Kövesdi Dorottya Gáti Róbert Sármay Gabriella
Pályázati támogatás:Bolyai Janos Kutatasi Osztondij
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

5.

001-es BibID:BIBFORM054320
Első szerző:Kurucz István
Cím:Bacterially expressed human FcγRIIb is soluble and functionally active after in vitro refolding / István Kurucz, Ágnes Hilbert, Attila Kapus, Dávid Medgyesi, Gábor Koncz, Gabriella Sármay, Anna Erdei, János Gergely
Dátum:2000
ISSN:0165-2478
Megjegyzések:A recombinant soluble form of the human Fc gamma receptor was produced by engineering a cDNA construct containing the extracellular part of the mature protein. After expression in bacteria as inclusion body, the polypeptide was highly purified and was refolded in vitro with a method that was developed for the renaturation of immunoglobulin fragments. With this method oxidation of the disulfide bridges within the domains of the protein is done in the presence of an artificial 'chaperone' which protects the polypeptide molecules from unwanted protein-protein interactions thereby inhibiting the incorrect oxidation of the SH-groups, and misfolding of the protein. The refolded recombinant soluble Fc gamma RIIb showed several characteristics of the native receptor: (i) it was recognized by a series of monoclonal antibodies specific for, and in most cases produced against the native cell-surface receptor; (ii) it is bound to its ligand (the Fc-region of different immunoglobulins) under very diverse conditions; and (iii) it is competed strongly and specifically with the native cell surface receptor for both ligand and antibody binding in experiments with distinct read-outs; (iv) monoclonal antibodies produced against the recombinant protein specifically recognized Fc gamma RIIb on different cells. From these data it was concluded that the recombinant soluble Fc-receptor was in a native, functionally active form, and its function was not affected by the lack of glycosylation. (C) 2000 Elsevier Science B.V. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
soluble Fc gamma receptors
bacterial expression
refolding
Megjelenés:Immunology Letters. - 75 : 1 (2000), p. 33-40. -
További szerzők:Hilbert Ágnes Kapus Attila Medgyesi Dávid Koncz Gábor (1970-) (biológus, immunológus) Sármay Gabriella Erdei Anna Gergely János
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

6.

001-es BibID:BIBFORM054307
035-os BibID:PMID: 15081531
Első szerző:Medgyesi Dávid
Cím:Functional consequences of a MAPK docking site on human FcγRIIb / Dávid Medgyesi, Rita Sárközi, Gábor Koncz, Krisztina Arató, Györgyi Váradi, Gábor K. Tóth, Gabriella Sármay
Dátum:2004
ISSN:0165-2478
Megjegyzések:Type IIb Fcgamma receptors (FcgammaRIIb) have a major role in regulating B cell activation. Upon its co-aggregation with the B cell receptors (BCR) via immune complexes FcgammaRIIb become phosphorylated on tyrosine within its immunoreceptor tyrosine based inhibitory motif (MM) and in turn recruit protein- and inositol phosphatases, inhibiting thereby signal transduction. The intracellular domain of the human FcgammaRIIb has a membrane proximal motif that is very similar to those of MAPK docking site in MAPK-interacting molecules. Additionally, in contrast to the mouse, a serine residue is located next to this motif that is a potential phosphorylation site for Ser/Thr kinases. Our aim was to study the role of the putative MAPK docking motif on FcgammaRIIb mediated function. We report here that MAPKs bind to FcgammaRIIb affinity purified from the detergent extracts of anti-IgM activated and BCR-FcgammaRIIb co-clustered B cells. We detected extracellular signal regulated kinase (ERK) activity in FcgammaRIIb immunoprecipitates and identified the bound proteins as 85, 44 and 42 kDa ERKs by Western blots. Active ERKs bound to the synthetic peptide representing the putative docking site of FcgammaRIIb on a Ser/Thr phosphatase dependent manner. The FcgammaRIIb-associated ERKs may phosphorylate the membrane proximal serine of the receptor. We examined the consequences of serine phosphorylation by comparing the proteins that interact with synthetic peptides comprising the combined sequences of the MAPK docking site and the ITIM either in phosphorylated or in non-phosphorylated forms. The results indicate that phosphorylation on serine modifies the binding of Lyn to FcgammaRIIb, thus might negatively regulate phosphorylation of ITIM. (C) 2003 Elsevier B.V. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
B cell
Fc gamma RIIb
MAPK docking site
regulation
signalling
Megjelenés:Immunology Letters. - 92 : 1-2 (2004), p. 83-90. -
További szerzők:Sárközi Rita Koncz Gábor (1970-) (biológus, immunológus) Arató Krisztina Váradi Györgyi Tóth Gábor K. Sármay Gabriella
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

7.

001-es BibID:BIBFORM054331
035-os BibID:PMID: 7797241
Első szerző:Sármay Gabriella
Cím:Interaction of signaling molecules with human FcγRIIb1 and the role of various FcγRIIb isoforms in B-cell regulation / Gabriella Sarmay, Zoltan Rozsnyay, Gabor Koncz, Janos Gergely
Dátum:1995
ISSN:0165-2478
Megjegyzések:The low-affinity type-IIb IgG Fc-binding receptors (Fc gamma RIIb) are expressed on B cells. When cross-linked with mIgM Fc gamma RIIb are known to down-regulate B-cell activation by interrupting signal transduction upstream from G-protein-activated events. We have studied Fc gamma RII isoforms expressed on resting and activated B cells and the interaction of Fc gamma RIIb1 with molecules transducing the antigen receptor-mediated signals. Expression of Fc gamma RII isoforms was studied by reverse transcription and polymerase chain reaction. Resting B cells express both Fc gamma RIIb2 and Fc gamma RIIb1 isoforms. Activation with anti-IgM or IL-4 induces the splicing of Fc gamma RIIb1 mRNA, while the alternative splicing of Fc gamma RIIb2 mRNA is down-regulated, resulting in the surface expression of Fc gamma RIIb1. Functional differences were found between the two isoforms in-inhibiting B-cell activation, suggesting that Fc gamma RIIb2 might influence the threshold of signals necessary for activation of resting B cells, while Fc gamma RIIb1 may regulate in later phases of antibody response.To explore the mechanism by which Fc gamma RII may uncouple antigen receptor-mediated signal transduction, we have investigated the association of signaling molecules with Fc gamma RII. Beside the protein tyrosine kinase (PTK) fyn, protein kinase C (PKC) was found to be co-isolated with Fc gamma RIIb1, suggesting a tight connection between these kinases and Fc gamma RII. We suggest that PKC might be responsible for the activation-induced phosphorylation of Fc gamma RII on serine residues. Signaling molecules responsible for the activation and localization of further elements of the activation pathway were also found to associate with Fc gamma RII. Among these RasGAP and Shc, the adapter molecule connecting PTK-triggered events to the Ras activation-dependent pathway were characterized. We suggest that Fc gamma RII may compete with the B-cell antigen receptor for key molecules regulating Ras activity, inhibiting thereby Ras activation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
HUMAN LYMPHOCYTES-B
RECEPTOR
PROTEIN
PHOSPHORYLATION
EXPRESSION
ACTIVATION
Megjelenés:Immunology Letters. - 44 : 2-3 (1995), p. 125-131. -
További szerzők:Rozsnyay Zoltán Koncz Gábor (1970-) (biológus, immunológus) Gergely János
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

8.

001-es BibID:BIBFORM054325
035-os BibID:PMID: 9052860
Első szerző:Sármay Gabriella
Cím:Integration of activatory and inhibitory signals in human B-cells / Gabriella Sármay, Gábor Koncz, János Gergely
Dátum:1996
ISSN:0165-2478
Megjegyzések:Fc gamma receptors type IIb1 (Fc gamma RIIb1) inhibit B-cell activation when co-ligated with B-cell antigen receptors (BCR) by immune complexes. In murine B-cells the inhibition is mediated by the interaction of the phosphorylated immunoreceptor tyrosine-based inhibitory motif (P-ITIM) of Fc gamma RIIb1 with the SH2 domain containing protein tyrosine phosphatase, SHP1. To clarify the mechanism of Fc gamma RIIb mediated inhibition of human B-cells we have studied the association of signaling molecules with human Fc gamma RIIb1 after co-ligating with BCR. Fc gamma RIIb1 were affinity purified from the Burkitt lymphoma cell line, BL41. Several tyrosine phosphorylated proteins were co-isolated with Fc gamma RIIb1 at 145, 110, and 50-60 kDa, which were not present in Fc gamma RIIb1 free immune complexes. Among these molecules we have identified the p52 She adaptor protein. Furthermore, we have shown that the insolubilised synthetic peptide corresponding P-ITIM bound She, Lyn and the p75 and p110 unidentified tyrosine phosphorylated proteins. Here we describe that the cell membrane associated She is partially dephosphorylated in BCR-Fc gamma RIIb1 co-ligated samples, suggesting that its function in regulating p21ras monomeric G protein is impaired. Indeed, we have detected a lower p21ras activity in BCR-Fc gamma RIIb1 co-crosslinked samples. These data indicate that co-ligation of BCR and Fc gamma RIIb1 interrupts signal transduction between protein tyrosine kinase activation and p21ras mediated activation pathway. Since in contrast to the mouse B-cells both Fc gamma RIIb1 and Fc gamma RIIb2 are expressed in human B-cells, we have investigated the inhibitory function of the two receptors in Fc gamma RIIb negative Burkitt lymphoma cell line ST486 transfected with Fc gamma RIIb1 and Fc gamma RIIb2, respectively. Both Fc gamma RIIb1 and Fc gamma RIIb2 inhibited the rise of intracellular Ca2+ induced by the crosslinking of BCR. The rate of the inhibition depended on the ratio of the co-crosslinked receptors (BCR-Fc gamma RIIb1) to the crosslinked BCR (BCR-BCR). Co-crosslinking of the two receptors inhibited not only the capacitive Ca2+ entry but rather the total Ca2+ response in both Fc gamma RIIb1 and Fc gamma RIIb2 transfected human B-cells. CD19 represents the signal transduction unit of complement receptor, CR2 (CD21), and is responsible for the complement activating IgM-immune complex induced enhancement of B-cell activation. Co-crosslinking of CD19 and BCR was shown to enhance B-cell activation due to the recruitment of further signaling molecules to the activator complex by the phosphorylated tyrosine residues of CD19. Here we show a novel finding that co-ligation of CD19 with Fc gamma RIIb1 inhibits the CD19-induced upregulation of Ca2+ response. The results indicate that IgG plus complement containing immune complexes may inhibit B-cell activation in vivo, due to the Fc gamma RIIb1-mediated interruption of signal transduction via both BCR and CD19.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Fc gamma RIIb
human B-cells
regulation
signal transduction
Megjelenés:Immunology Letters. - 54 : 2-3 (1996), p. 93-100. -
További szerzők:Koncz Gábor (1970-) (biológus, immunológus) Gergely János
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM054324
035-os BibID:PMID: 9232445
Első szerző:Sármay Gabriella
Cím:Fcγ receptor type IIb induced recruitment of inositol and protein phosphatases to the signal transductory complex of human B-cell / Gabriella Sarmay, Gábor Koncz, Israel Pecht, János Gergely
Dátum:1997
ISSN:0165-2478
Megjegyzések:Co-clustering of Fc gamma RIIb and B-cell receptor (BCR) inhibits cell activation by interrupting BCR stimulated signal transduction. The immunoreceptor tyrosine-based inhibitory motif (ITIM) of Fc gamma RIIb becomes tyrosyl phosphorylated (P-ITIM) upon co-clustering with BCR then P-ITIM interacts with several signalling molecules, some of which negatively regulate the cell activation process. The molecules recruited by the P-ITIM of human Fc gamma RIIb have not been characterised yet. In order to affinity isolate the potential functional partner molecules of human Fc gamma RIIb, synthetic peptides were designed to cover almost the entire intracellular Fc gamma RIIb domain, including Fc gamma RIIb1 and Fc gamma RIIb2 specific sequences and stretches containing the phosphorylated and non-phosphorylated ITIM. We report here that several tyrosyl phosphorylated proteins bind to the P-ITIM peptide from both resting and activated B-cell lysates, the 53-56 kDa being the most prominent one. A fraction of the 53-56 kDa bands were identified as the protein tyrosine kinase (PTK), Lyn which also bound to ITIM peptide, pointing to its role in initiating Fc gamma RIIb-mediated negative regulation. Among the P-ITIM associated tyr phosphorylated components, the 145 kDa one was identified as the inositol polyphosphate 5-phosphatase, SHIP and the 72 kDa protein as the protein tyrosine phosphatase (PTP) SHP2; whereas SHP1 was not detected. Phosphatase activity assays showed that P-ITIM bound about five times higher SHIP and four times higher PTP activity than the ITIM containing peptide. Furthermore, we detected PKC and MAPK in both ITIM and P-ITIM peptides precipitated samples. Since human B-cells express both Fc gamma RIIb1 and Fc gamma RIIb2, differing in a 19 amino acid insert in the cytoplasmic tail of the former, we investigated the components binding to Fc gamma RIIb1 and Fc gamma RIIb2 specific sequences. Synthetic peptide representing Fc gamma RIIb1 and Fc gamma RIIb2 specific sequences weakly bound unidentified tyr phosphorylated proteins at 50-56 kDa, while the insert itself did not bind a detectable amount of protein. Neither of the ITIM or P-ITIM bound molecules were observed in samples precipitated with peptides corresponding to Fc gamma RIIb1 or Fc gamma RIIb2 specific sequences. These observations suggest that protein kinases associate with both ITIM and P-ITIM of human Fc gamma RIIb, Lyn being responsible for the tyrosyl phosphorylation of ITIM. SHIP and SHP2 phosphatases selectively bind to the phosphorylated ITIM. Based on these data we assume that SHIP and SHP2 recruited in vivo to the Fc gamma RIIb co-clustered BCR are responsible for the Fc gamma RIIb mediated negative regulation of human B-cell activation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
human B-lymphocytes
Fc gamma RIIb
phosphatases
signal transduction
regulation
Megjelenés:Immunology Letters. - 57 : 1-3 (1997), p. 159-164. -
További szerzők:Koncz Gábor (1970-) (biológus, immunológus) Pecht, Israel Gergely János
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

10.

001-es BibID:BIBFORM054322
Első szerző:Sármay Gabriella
Cím:Cooperation between SHP-2, phosphatidyl inositol 3-kinase and phosphoinositol 5-phosphatase in the FcγRIIb mediated B cell regulation / Gabriella Sármay, Gábor Koncz, Israel Pecht, János Gergely
Dátum:1999
ISSN:0165-2478
Megjegyzések:Go-clustering B cell receptors (BCR) and type II receptors binding the Fc part of IgG (Fc gamma RIIb) inhibits B cell activation and antibody production. Tyrosine phosphorylation of an intracellular motif of Fc gamma RIIb has been shown to be a prerequisite of the inhibition. After being phosphorylated by BCR-activated tyrosine kinases, the immunoreceptor tyrosine-based inhibitory motif (P-ITIM) of Fc gamma RIIb recruits SH2 domain containing protein tyrosine phosphatase(s) (PTPs) and polyphosphoinositol 5-phosphatase (SHIP) to the vicinity of BCR, which in turn dephosphorylate their specific substrates. This leads to the interruption of signal transduction, consequently to the anergy and/or apoptosis of the cell. The downstream signaling pathways affected by Fc gamma RIIb-BCR co-clustering are not clarified yet, neither the substrates of PTPs are known. We have studied the Fc gamma RIIb mediated B cell inhibition on human Burkitt lymphoma cell line (BL41). From the lysates of BL41 cells SHP-2 and phosphatidylinositol 3-kinase (PI3-K), as well as the protein tyrosine kinase (PTK) Lyn bind both to the BCR-co-clustered Fc gamma RIIb and to its P-ITIM peptide. Lyn hyperphosphorylates the P-ITIM associated molecules, including SHIP in the in vitro protein tyrosine kinase activity assay. The P-ITIM-compelled multi-phosphoprotein complex binds to and activates SHP-2, which in turn dephosphorylates SHIP and Shc and probably other substrates. Subcellular localisation of these signaling molecules is regulated by the phosphotyrosin-SH2 domain interactions, thus dephosphorylation may result in the re-direction of Shc and SHIP within the cell, consequently, in the modulation of their activity. Finally, co-clustering Fc gamma RIIb and BCR or Fc gamma RIIb and CD19 on the intact cells inhibited PI3-K activity as detected in the anti-phosphotyrosine (anti-PY) precipitates. The results indicate that SHP-2 bound to and activated by the BCR co-clustered Fc gamma RIIb, may down-regulate PI3-K activity by dephosphorylating a yet unidentified regulatory molecule, which recruits PI3-K to the cell membrane.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
human Fc gamma RIIb
B cell regulation
SHP-2
PI3-K
Megjelenés:Immunology Letters. - 68 : 1 (1999), p. 25-34. -
További szerzők:Koncz Gábor (1970-) (biológus, immunológus) Pecht, Israel Gergely János
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Rekordok letöltése1 
Corvina könyvtári katalógus v8.2.27 © 2023 Monguz kft. Minden jog fenntartva.