P2Y2 receptors induced cell surface redistribution of alpha(v) integrin is required for activation of ERK 1/2 in U937 cells.
Nucleotides released from cells due to stress, injury or inflammation, induce mitogenic effects in monocytes via activation of P2Y(2) nucleotide receptors (P2Y(2)Rs). Here we show that P2Y(2) nucleotide receptors in U937 monocytic cells regulate the activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) by inducing the clustering of alpha(v) integrins. The activation of phosphatidylinositol 3-kinase by P2Y(2)R ligands was required for alpha(v) clustering, suggesting a means whereby two different classes of receptors communicate to induce mitogenic responses in monocytic cells. P2Y(2)R-induced alpha(v) clustering was also associated with a flattened phenotype of the U937 cells, consistent with the role of the P2Y(2)R in regulating early events in cell migration.
Chorna
Nataliya E
NE
Department of Chemistry, Río Piedras Campus, University of Puerto Rico, San Juan, Puerto Rico, USA.
Chevres
Migdalia
M
Santos-Berrios
Cynthia
C
Orellano
Elsie A
EA
Erb
Laurie
L
González
Fernando A
FA
D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger / Q000378:metabolism; D011940:Receptor Aggregation; D020239:Receptor Cross-Talk; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2; D013997:Time Factors; D020298:U937 Cells; D014544:Uridine Triphosphate / Q000378:metabolism* / Q000494:pharmacology
D039564:Integrin alphaV; C546385:P2RY2 protein, human; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium; D014544:Uridine Triphosphate