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G E Liwszyc

Publications and source records attributed to G E Liwszyc.

4 recordsLinked to original sources
PubMed1998

Signalling initiated with CD4-TCR or TCR-TCR interactions: comparison of tyrosine phosphorylation patterns and CD45 effects.

Antigen-triggered response in T cells is mediated by the T cell receptor (TCR)/CD3-complex. This signalling, however, is modulated by a number of other surface molecules. Among the most important of these is the CD4/CD8 molecule which associates with the TCR/CD3-complex and binds to the MHC complex. The molecular mechanisms involved in interactions between TCR-TCR and TCR-CD4 are not fully understood. We have earlier described an experimental model that allows us to dissect signals involving CD4-TCR interactions and those involving TCR-TCR interactions using a mouse CD4-CD8- T cell hybridoma cell-line transfected either with the TCR from a mouse T-helper 2 cell-line (D10) alone or with both the TCR and the CD4 molecule. To further characterize these two different modes of signalling in T lymphocytes we have studied the tyrosine phosphorylation patterns resulting from these interactions. In addition, we have studied the modulatory effect of the CD45 molecule on these interactions. In contrast to some earlier reports, we found that both the patterns of induced tyrosine phosphorylation and the effects of CD45 modulation were essentially similar in the CD4-TCR and the TCR-TCR signal transduction cascades. The results are consistent with a purely synergistically amplifying function for CD4 on the TCR-mediated signalling.

Animals↗
PubMed1998

p72syk protein tyrosine kinase: an early transducer of sIgG-triggered apoptotic signalling in human follicular lymphoma cells.

Cross-linking of B cell antigen receptor (sIg) elicits different biological responses, including cell activation, proliferation, differentiation, anergy and cell death depending on the maturational stage of the cell. We established the tumor cell lines HF-1.3.4 and HF-4-9 from two patients with follicular lymphoma. Both cell lines carry the characteristic t(14;18) chromosomal translocation and display constitutively overexpressed Bcl-2. HF-1.3.4 represents a mature B cell with sIgG and several somatic hypermutations in its Ig genes, while HF-4-9 is a less mature B cell, expressing sIgM and only a few mutations in its Ig genes. Cross-linking of sIg with antibodies leads to apoptosis in HF-1.3.4 cells but not in HF-4-9 cells. Triggering of sIg induced, within seconds, identical tyrosine phosphorylation of p53/56lyn protein tyrosine kinase (PTK) and p55blk PTK in both of the cell lines; however, a prominent tyrosine phosphorylation and activation of p72syk PTK only in HF-1.3.4 cells. We conclude that p72syk PTK is of importance in relaying apoptotic signalling upon sIg cross-linking in the HF-1.3.4 cell line. Given the mature phenotype of the HF-1.3.4 cell line it serves as a model for the late negative selection during B cell ontogeny. Moreover, our results question the current concept that a constitutive overexpression of BcI-2 confers resistance to sIg ligation-induced apoptosis in lymphoma cells.

Apoptosis↗
PubMed1994

Triggering of human natural killer cells through CD16 induces tyrosine phosphorylation of the p72syk kinase.

Activation of protein tyrosine kinases (PTK) is an initial and obligatory event for the triggering of human natural killer (NK) cells to cytotoxicity. Of the different PTK detected in NK cells, only p56lck has previously been shown to participate in NK cell activation. Here we present evidence that another PTK, p72syk, is involved in activation of NK cells. Stimulation with a monoclonal antibody to to the Fc gamma RIII receptor (CD16) induced an increased tyrosine phosphorylation of p72syk. This phosphorylation correlated with an increased tyrosine kinase activity of p72syk towards a synthetic peptide substrate. A severalfold increase in the catalytic activity of p72syk was also seen after treatment of NK cells with an inhibitor of phosphotyrosine phosphatases, pervanadate. We conclude that triggering of the cytotoxic response in NK cells is associated with activation of p72syk.

Amino Acid Sequence↗