scholarly journals Syk and Bruton's Tyrosine Kinase Are Required for B Cell Antigen Receptor-mediated Activation of the Kinase Akt

1999 ◽  
Vol 274 (43) ◽  
pp. 30644-30650 ◽  
Author(s):  
Andrew Craxton ◽  
Aimin Jiang ◽  
Tomohiro Kurosaki ◽  
Edward A. Clark
FEBS Letters ◽  
2002 ◽  
Vol 514 (2-3) ◽  
pp. 260-262 ◽  
Author(s):  
Kazunori Inabe ◽  
Toshio Miyawaki ◽  
Richard Longnecker ◽  
Hiroyoshi Matsukura ◽  
Satoshi Tsukada ◽  
...  

1996 ◽  
Vol 184 (1) ◽  
pp. 31-40 ◽  
Author(s):  
M Takata ◽  
T Kurosaki

Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-gamma 2 activation. Since Syk is also required for the BCR-induced PLC-gamma 2 activation, our findings indicate that PLC-gamma 2 activation is regulated by Btk and Syk through their concerted actions.


Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2357-2364 ◽  
Author(s):  
Shoji Hashimoto ◽  
Akihiro Iwamatsu ◽  
Masamichi Ishiai ◽  
Katsuya Okawa ◽  
Tomoki Yamadori ◽  
...  

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.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3536-3536
Author(s):  
Naohide Watanabe ◽  
Hideaki Nakajima ◽  
Atsushi Oda ◽  
Yasuo Ikeda ◽  
Makoto Handa

Abstract Phosphoinositide 3-kinase (PI3K)-dependent activation of Bruton’s tyrosine kinase (Btk) is an indispensable step of B cell antigen receptor (BCR)-mediated signaling leading to cell development and function. Btk is a cytosolic tyrosine kinase and its recruitment to the plasma membrane is a necessary step for its function. In the BCR pathway, class 1A PI3K is though to play a major role in Btk recruitment by generating the D3 phosphoinositide as a docking site for the pleckstrin homology (PH) domain of this effecter kinase. This widely accepted hypothesis has been tested in platelets from gene knockout or mutant mice, since the cells utilize sets of transducers in collagen-induced GP VI signaling similar to those involved in immunoreceptor tyrosine-based activation motif-mediated signaling cascades activated by BCR and T cell antigen receptor (TCR) ligation. GP VI stimulation by collagen or collagen related peptide induces cellular responses including aggregation, granular secretion and adhesion, and Btk/phospholipase C (PLC) γ2 activation. As compared with control mice, these cellular responses and PLCγ2 tyrosine phosphorylation of either Btk or PI3K p85α−/− platelets were readily impaired, but the defect was greater in Btk−/− than p85α−/− platelets. Most strikingly, platelets from double-deficiency mice showed a most severely compromised phenotype implying the existence of a PI3K-independent pathway for Btk activation. Moreover, unlike B cells, as compared with Btk−/− platelets, only subtle functional defect was observed in X-linked immunodeficiency (Xid) platelets in which PI3K-dependent Btk activation is selectively lacking due to a naturally occurring point mutation of the gene encoding the PH domain of the kinase. In the TCR pathway, an adaptor complex formed by LAT, Gads and SLP-76 proteins that is membrane-bound via LAT palmitoylation readily recruits Itk, which is a counterpart Btk/Tec family kinase specific for TCR. Indeed, Btk was found to be associated with LAT/Gads/SLP-76 complex in platelets in a GP VI-stimulation dependent manner, and this phenomenon was unaffected by either PI3K defect or PI3K inhibitor. These results indicate that in platelet immunoreceptor signaling, Btk function is under control, at least in part, by a mechanism independent of PI3K engagement.


Science ◽  
1991 ◽  
Vol 251 (4990) ◽  
pp. 192-194 ◽  
Author(s):  
Y Yamanashi ◽  
T Kakiuchi ◽  
J Mizuguchi ◽  
T Yamamoto ◽  
K Toyoshima

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