scholarly journals B cell antigen receptor-induced plasma membrane recruitment of the SH2 domain-containing inositol phosphatase is mediated by the protein tyrosine kinases Lyn and Syk

2009 ◽  
Vol 7 (S1) ◽  
Author(s):  
M Engelke ◽  
X Li ◽  
B Manno ◽  
K Neumann ◽  
J Wienands
Keyword(s):  
Plasma Membrane ◽  
B Cell ◽  
Tyrosine Kinases ◽  
Sh2 Domain ◽  
Protein Tyrosine Kinases ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Membrane Recruitment ◽  
Cell Antigen ◽  
Inositol Phosphatase

scholarly journals TAPP1 and TAPP2 Are Targets of Phosphatidylinositol 3-Kinase Signaling in B Cells: Sustained Plasma Membrane Recruitment Triggered by the B-Cell Antigen Receptor

2002 ◽  
Vol 22 (15) ◽  
pp. 5479-5491 ◽  
Author(s):  
Aaron J. Marshall ◽  
Allyson K. Krahn ◽  
Kewei Ma ◽  
Vincent Duronio ◽  
Sen Hou
Keyword(s):  
Plasma Membrane ◽  
B Cell ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Ph Domain ◽  
Phosphatidylinositol 3 Kinase ◽  
Cell Antigen Receptor ◽  
Membrane Recruitment ◽  
Cell Antigen ◽  
Phosphatidylinositol 3

ABSTRACT We report the characterization of two signal transduction proteins related to Bam32, known as TAPP1 and TAPP2. Bam32, TAPP1, and TAPP2 share several characteristics, including small size (32 to 47 kDa), lack of enzymatic domains, high conservation between humans and mice, and the presence of pleckstrin homology (PH) domains near their C termini which contain the 3-phosphoinositide-binding motif. Unlike Bam32, the N-terminal regions of TAPP1 and TAPP2 contain a second PH domain. TAPP1 and TAPP2 transcripts are expressed in a variety of tissues including lymphoid tissues. Using live-cell imaging, we demonstrate that TAPP1 and TAPP2 are recruited to the plasma membrane of BJAB human B-lymphoma cells upon activation through the B-cell antigen receptor (BCR). The C-terminal PH domain is necessary and sufficient for BCR-induced membrane recruitment of both TAPP1 and TAPP2. Blockade of phosphatidylinositol 3-kinase (PI3K) activity completely abolished BCR-induced recruitment of TAPP1 and TAPP2, while expression of active PI3K is sufficient to drive constitutive membrane localization of TAPP1 and TAPP2. TAPP1 and TAPP2 preferentially accumulate within ruffled, F-actin-rich areas of plasma membrane, suggesting a potential role in PI3K-driven cytoskeletal reorganization. Like Bam32, BCR-driven TAPP1 and TAPP2 recruitment is a relatively slow and sustained response, in contrast to Btk recruitment and Ca2+ mobilization responses, which are rapid and transient. Consistent with recent studies indicating that Bam32, TAPP1, and TAPP2 can bind to PI(3,4)P2, we find that membrane recruitment correlates well with production of PI(3,4)P2 but not with that of PI(3,4,5)P3. Our results indicate that TAPP1 and TAPP2 are direct targets of PI3K signaling that are recruited into plasma membranes with distinctive delayed kinetics and accumulate within F-actin-rich membrane ruffles. We postulate that the TAPPs function to orchestrate cellular responses during the sustained phase of signaling.

B-cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn

1993 ◽  
Vol 3 (10) ◽  
pp. 645-657 ◽  
Author(s):  
Debbie A. Law ◽  
Vivien W.F. Chan ◽  
Sandip K. Datta ◽  
Anthony L. DeFranco
Keyword(s):  
B Cell ◽  
Tyrosine Kinases ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Identification of the SH2 Domain Binding Protein of Bruton’s Tyrosine Kinase as BLNK—Functional Significance of Btk-SH2 Domain in B-Cell Antigen Receptor-Coupled Calcium Signaling

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2357-2364 ◽  
Author(s):  
Shoji Hashimoto ◽  
Akihiro Iwamatsu ◽  
Masamichi Ishiai ◽  
Katsuya Okawa ◽  
Tomoki Yamadori ◽  
...  
Keyword(s):  
B Cells ◽  
Tyrosine Kinase ◽  
Calcium Signaling ◽  
B Cell ◽  
Functional Significance ◽  
Antigen Receptor ◽  
Sh2 Domain ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen

Bruton’s tyrosine kinase (Btk) is a critical component in the B-cell antigen receptor (BCR)-coupled signaling pathway. Its deficiency in B cells leads to loss or marked reduction in the BCR-induced calcium signaling. It is known that this BCR-induced calcium signaling depends on the activation of phospholipase Cγ (PLCγ), which is mediated by Btk and another tyrosine kinase Syk and that the SH2 and pleckstrin homology (PH) domains of Btk play important roles in this activation process. Although the importance of the PH domain of Btk has been explained by its role in the membrane targeting of Btk, the functional significance of the SH2 domain in the calcium signaling has remained merely a matter of speculation. In this report, we identify that one of the major Btk-SH2 domain-binding proteins in B cells is BLNK (B-cell linker protein) and present evidences that the interaction of BLNK and the SH2 domain of Btk contributes to the complete tyrosine phosphorylation of PLCγ.

scholarly journals Regulation of RasGRP1 by B Cell Antigen Receptor Requires Cooperativity between Three Domains Controlling Translocation to the Plasma Membrane

2007 ◽  
Vol 18 (8) ◽  
pp. 3156-3168 ◽  
Author(s):  
Nadine Beaulieu ◽  
Bari Zahedi ◽  
Rebecca E. Goulding ◽  
Ghazaleh Tazmini ◽  
Kira V. Anthony ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
B Cell ◽  
Antigen Receptor ◽  
Cell Types ◽  
Membrane Localization ◽  
Membrane Targeting ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
C1 Domain

RasGRP1 is a Ras-activating exchange factor that is positively regulated by translocation to membranes. RasGRP1 contains a diacylglycerol-binding C1 domain, and it has been assumed that this domain is entirely responsible for RasGRP1 translocation. We found that the C1 domain can contribute to plasma membrane-targeted translocation of RasGRP1 induced by ligation of the B cell antigen receptor (BCR). However, this reflects cooperativity of the C1 domain with the previously unrecognized Plasma membrane Targeter (PT) domain, which is sufficient and essential for plasma membrane targeting of RasGRP1. The adjacent suppressor of PT (SuPT) domain attenuates the plasma membrane-targeting activity of the PT domain, thus preventing constitutive plasma membrane localization of RasGRP1. By binding to diacylglycerol generated by BCR-coupled phospholipase Cγ2, the C1 domain counteracts the SuPT domain and enables efficient RasGRP1 translocation to the plasma membrane. In fibroblasts, the PT domain is inactive as a plasma membrane targeter, and the C1 domain specifies constitutive targeting of RasGRP1 to internal membranes where it can be activated and trigger oncogenic transformation. Selective use of the C1, PT, and SuPT domains may contribute to the differential targeting of RasGRP1 to the plasma membrane versus internal membranes, which has been observed in lymphocytes and other cell types.

scholarly journals The Dynamics of Protein Kinase B Regulation during B Cell Antigen Receptor Engagement

1999 ◽  
Vol 145 (7) ◽  
pp. 1511-1520 ◽  
Author(s):  
Emmanuelle Astoul ◽  
Sandra Watton ◽  
Doreen Cantrell
Keyword(s):  
Plasma Membrane ◽  
B Cells ◽  
Protein Kinase ◽  
B Cell ◽  
B Lymphocytes ◽  
Protein Kinase B ◽  
B Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Sustained Activation

This study has used biochemistry and real time confocal imaging of green fluorescent protein (GFP)-tagged molecules in live cells to explore the dynamics of protein kinase B (PKB) regulation during B lymphocyte activation. The data show that triggering of the B cell antigen receptor (BCR) induces a transient membrane localization of PKB but a sustained activation of the enzyme; active PKB is found in the cytosol and nuclei of activated B cells. Hence, PKB has three potential sites of action in B lymphocytes; transiently after BCR triggering PKB can phosphorylate plasma membrane localized targets, whereas during the sustained B cell response to antigen, PKB acts in the nucleus and the cytosol. Membrane translocation of PKB and subsequent PKB activation are dependent on BCR activation of phosphatidylinositol 3-kinase (PI3K). Moreover, PI3K signals are both necessary and sufficient for sustained activation of PKB in B lymphocytes. However, under conditions of continuous PI3K activation or BCR triggering there is only transient recruitment of PKB to the plasma membrane, indicating that there must be a molecular mechanism to dissociate PKB from sites of PI3K activity in B cells. The inhibitory Fc receptor, the FcγRIIB, mediates vital homeostatic control of B cell function by recruiting an inositol 5 phosphatase SHIP into the BCR complex. Herein we show that coligation of the BCR with the inhibitory FcγRIIB prevents membrane targeting of PKB. The FcγRIIB can thus antagonize BCR signals for PKB localization and prevent BCR stimulation of PKB activity which demonstrates the mechanism for the inhibitory action of the FcγRIIB on the BCR/PKB response.

scholarly journals Role of Tyrosine Phosphorylation of HS1 in B Cell Antigen Receptor-mediated Apoptosis

1997 ◽  
Vol 185 (7) ◽  
pp. 1387-1392 ◽  
Author(s):  
Yuji Yamanashi ◽  
Takahiro Fukuda ◽  
Hirofumi Nishizumi ◽  
Tetsuya Inazu ◽  
Ken-ichi Higashi ◽  
...  
Keyword(s):  
B Cell ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Nuclear Translocation ◽  
Antigen Receptor ◽  
B Cell Antigen Receptor ◽  
Wild Type ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Induced Apoptosis

The 75-kD HS1 protein is highly tyrosine-phosphorylated during B cell antigen receptor (BCR)-mediated signaling. Owing to low expression of HS1, WEHI-231-derived M1 cells, unlike the parental cells, are insensitive to BCR-mediated apoptosis. Here, we show that BCR-associated tyrosine kinases Lyn and Syk synergistically phosphorylate HS1, and that Tyr378 and Tyr-397 of HS1 are the critical residues for its BCR-induced phosphorylation. In addition, unlike wild-type HS1, a mutant HS1 carrying the mutations Phe-378 and Phe-397 was unable to render M1 cells sensitive to apoptosis. Wild-type HS1, but not the mutant, localized to the nucleus under the synergy of Lyn and Syk. Thus, tyrosine phosphorylation of HS1 is required for BCR-induced apoptosis and nuclear translocation of HS1 may be a prerequisite for B cell apoptosis.

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