ERK AND AKT ACTIVATION VIA CD150: SIGNAL TRANSDUCTION STUDIES ON DT40 CELL LINE MODEL SYSTEM

Mikhalap S.V., Shlapatska L.M., Berdova A.G., Yurchenko M.Yu., Clark E.A., Chekhun V.F., Sidorenko S.P.

CD150 is a cell surface receptor that belongs to the CD2 subfamily of immunoglobulin suprefamily. CD150 functions are linked with the presence of paired tyrosine-based motif TxYxxV/I in CD150 cytoplasmic tail. This motif could bind a different SH2-containing signal transduction molecules, including tyrosine and inositol phosphatases, Src family kinases, and also adaptor molecules SH2D1A and EAT-2. In this work, the DT40 chicken B lymphoma cell lines, transfected with CD150 alone or together with the adaptor protein SH2D1A, were used to analyze the signal transduction pathways, which are linked to CD150 and regulated by the adaptor protein SH2D1A. CD150 ligation on both transfectants initiated Ras pathway (ERK1/2 activation), but did not trigger Rac-mediated pathway (JNK1/2 and p38 MAPK). Transfection of the adaptor protein SH2D1A into DT40 cells that express CD150 resulted in: 1) elevation of BCR-initiated tyrosine phosphorylation of intracellular substrates and Ca2+ mobilization, 2) tyrosine phosphorylation of 52–55 kDa band in respond to CD150 ligation, and 3) CD150-mediated activation of Akt/PKB. Since SH2D1A is a product of the gene that is mutated in X-linked lymphoproliferative disorder, B cell non-Hodgkin’s lymphoma and familial hemophagocytic lymphohistiocytosis, these data are very important for understanding the molecular basis of the regulation of signal transduction pathways via the receptors with TxYxxV/I motif in normal and leukemic lymphocytes.

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