HER2 (human epidermal growth factor receptor-2; also known as erbB2) and its relatives HER1 (epidermal growth factor receptor; EGFR), HER3 and HER4 belong to the HER family of receptor tyrosine kinases. In normal cells, activation of this receptor ty
Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells and interstitial cells of Cajal (ICCs). Mice and rats with a double gene dose of loss-of-function mutations of Kit show de
Protein tyrosine phosphorylation plays an important role in cell growth, development and oncogenesis. No classical protein tyrosine kinase has hitherto been cloned from plants. Does protein tyrosine kinase exist in plants? To address this, we have pe
FLT3, a member of the class III receptor tyrosine kinases (RTKs), is preferentially expressed on the cell surface of hematopoietic progenitors, and the ligand of FLT3 (FL) is expressed as a membrane-bound or soluble form by bone marrow stroma cells.
Inositol polyphosphatases (IPPases), particularly those that can hydrolyze myo-inositol hexakisphosphate (Ins P6), are of biotechnological interest for their ability to reduce the metabolically unavailable organic phosphate content of feedstuffs and
T-cell protein tyrosine phosphatase (TCPTP/TC45) is a ubiquitously expressed intra-cellular non-receptor protein tyrosine phosphatase involved in the negative regulation of several cancer relevant cellular signalling pathways. We have previously show
Immature B lymphocytes and certain B cell lymphomas undergo apoptotic cell death following activation of the B cell antigen receptor (BCR) signal transduction pathway. Several biochemical changes occur in response to BCR engagement, including activat
The receptor-type protein tyrosine phosphatase PTPσ mediates neural development and regeneration. Early studies on the ligands of PTPσ identified heparan sulfate proteolycan (HSPG) as a ligand. Binding of HSPG to PTPσ plays a critical role in axon gu
Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of insulin signaling and adiposity and is a drug target for the treatment of obesity and diabetes. The molecular mechanisms underlying PTP1B metabolic actions require additional inv
Many oncogenes encode protein tyrosine kinases (PTKs). Oncogenic mutations of these genes invariably result in constitutive activation of these PTKs. Autophosphorylation of the PTKs and tyrosine phosphorylation of their cellular substrates are essent
Cell Communication and Signaling
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 M Engelke*, X Li, B Manno, K Neumann and J Wienands Address: University of Goettingen, Cellular and Molecular Immunology, Göttingen, Germany * Corresponding author
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 Published: 26 February 2009 Cell Communication and Signaling 2009, 7(Suppl 1):A73
12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar JanssenMeeting abstracts – A single PDF containing all abstracts in this Supplement is available here.
Signals transduced by the B cell antigen receptor (BCR) are essential for B cell development and activation. Precise regulation of BCR signals is required to provide antigenspecific humoral immunity on one hand and tolerance of self proteins on the other hand. The SH2 domain-containing inositol 5' phosphatase (SHIP) is an important component for limiting antigen-induced signals in B cells. SHIP hydrolyzes the 5' phosphate of phosphatidyl-3,4,5trisphosphate (PIP3) at the inner leaflet of the plasma membrane thereby disrupting binding motifs for the plextrine homology domains and attenuating the activities of Bruton's tyrosine kinase and phospholipase C-γ (PLC-γ2), respectively. Initially SHIP activation was believed to depend on inhibitory coreceptors like the Fc-γRIIB. However, studies using ship-/- DT40 cells or mice revealed that SHIP is activated downstream of BCR engagement in absence of Fcγ-RIIb also. The mechanism of BCR-induced SHIP activation and its relocalization towards the substrate PIP3, however, remains obscure to date. Here we report a real time imaging approach to analyze the molecular mechanism of BCR-induced SHIP relocalization. Interestingly, neither Fcg-RIIb nor the SHIP SH2 domain contributed to this process. Using genetic variants of DT40 B cells we could show that SHIP plasma membrane recruitment occurs upstream of PLC-γ2 activation. Our studies revealed that two apparently independent mechanisms are involved. First the Lyn-dependent assembly of a trimolecular complex comprising SHIP, the SH2 domaincontaing adapter protein (Shc) and the growth factor receptor-bound protein 2 (Grb2) supports the SHIP relo-
calization. Second, the protein tyrosine kinase Syk is required for efficient SHIP plasma membrane recruitment.
Page 1 of 1 (page number not for citation purposes)