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- Title
Signal transduction and white cell maturation via extracellular ATP and the P2Y[sub 11] receptor.
- Authors
Weyden, Louise Van Der; Conigrave, Arthur D; Morris, Michael B
- Abstract
Extracellular ATP promotes a wide range of physiological effects in many tissues. Of particular interest is the effect of ATP on leukaemia-derived HL-60 and NB4 cell lines, which are induced to mature to neutrophil-like cells. The differentiation process appears to be mediated by ATP binding to a cell-surface purinergic P2Y receptor, resulting in the stimulation of adenylyl cyclase, elevation of cAMP levels and activation of protein kinase A. In 1997, a novel ATP-selective P2Y receptor, P2Y[sub 11], was cloned and shown to be linked to both cAMP and Ca[sup 2+] signalling pathways. The pharmacological profile of ATP analogues used by P2Y[sub 11] for cAMP production in transfected cells is reviewed in the present paper and shown to be closely similar to the profiles for cAMP production and differentiation of myeloblastic HL-60 cells and promyelocytic NB4 cells, both of which express P2Y[sub 11]. Additional data are provided showing that HL-60 mature to neutrophil-like cells in response to extracellular ATP, as measured by upregulation of the N-formyl peptide receptor, N-formyl peptide-mediated actin polymerization and superoxide production. It is proposed that P2Y[sub 11] is responsible for the ATP-mediated differentiation of these cells lines and that this receptor may play a role in the maturation of granulocytic progenitors in the bone marrow.
- Subjects
ADENOSINE triphosphate; CELLULAR signal transduction; LEUCOCYTES
- Publication
Immunology & Cell Biology, 2000, Vol 78, Issue 4, p369
- ISSN
0818-9641
- Publication type
Article
- DOI
10.1046/j.1440-1711.2000.00918.x