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Signal transduction and white cell maturation via extracellular ATP and the P2Y 11 receptor
Author(s) -
Van Der Weyden Louise,
Conigrave Arthur D,
Morris Michael B
Publication year - 2000
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.2000.00918.x
Subject(s) - p2y receptor , microbiology and biotechnology , purinergic receptor , extracellular , signal transduction , biology , receptor , biochemistry
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 11 , was cloned and shown to be linked to both cAMP and Ca 2+ signalling pathways. The pharmacological profile of ATP analogues used by P2Y 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 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 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.