EVIDENCE FOR PROTEIN-KINASE-C - INDEPENDENT PATHWAYS MEDIATING PHORBOL ESTER INDUCED PLASMACYTOID DIFFERENTIATION OF B-CHRONIC LYMPHOCYTIC-LEUKEMIA CELLS

被引:14
作者
MURPHY, JJ
YAXLEY, JC
NORTON, JD
机构
[1] Department of Haematology, Royal Free Hospital School of Medicine, Hampstead, London
关键词
PROTEIN KINASE-C; PHORBOL ESTER; LYMPHOCYTE-B DIFFERENTIATION;
D O I
10.1016/0167-4889(91)90184-Y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effects of phorbol esters on many cell types are known to be mediated through activation of the protein kinase C (PKC) signal transduction pathway. By using the specific inhibitor of this enzyme 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine dihydrochloride (H7) we have assessed the role of PKC activation in phorbol ester (phorbol 12-myristate 13-acetate, PMA)-induced plasmacytoid differentiation of B chronic lymphocytic leukemia cells (B-CLL) as a model of terminal differentiation of human B lymphocytes. H7 affected a dose-dependent inhibition of PMA-induced thymidine and uridine uptake with ID50 values of 41-mu-M and 32-mu-M, respectively. A comparable ID50 value (34-mu-M) was obtained for H7 inhibition of B-CLL PKC activity in a cell-free system. PMA-induced changes in cell morphology, expression of CD20, CD37 and FMC7 surface antigens together with increased secretion of immunoglobulin were variably abrogated by H7 suggesting that PKC activation is more important in B cell activation/DNA synthesis than in the differentiative response. Consistent with this, expression of a sizable proportion of PMA-inducible genes was not significantly affected by H7. These data are consistent with the existence of a PMA-activated, PKC-independent signal transduction pathway which may be important, though by itself apparently insufficient, for eliciting full terminal differentiation in B lymphocytes.
引用
收藏
页码:110 / 118
页数:9
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