An essential role for calmodulin in regulating human T cell aggregation.
After activation of T cells with either CD3 antibodies or phorbol esters, we have found that T cell-cell aggregation, integrin-dependent actin reorganisation and cell spreading are strongly suppressed by any of three structurally different calmodulin antagonists, without any effect on the amount of CD11/CD18 integrin binding to the actin cytoskeleton. However, only T cell receptor-induced, and not phorbol ester-induced, aggregation and cell spreading are prevented by inhibitors of phosphatidylinositide (PI) 3-kinase. These results suggest that PI 3-kinase lies upstream of calmodulin in the signalling pathway leading to T cell aggregation, cell spreading and actin reorganisation and that cell spreading and actin reorganisation are essential for T cell adhesion.
Medical Research Council Protein Phosphorylation Unit, University of Dundee, Dundee DD1 5EH, UK. s.c.fagerholm@dundee.ac.uk
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Fagerholm
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Prescott
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Cohen
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Gahmberg
D000199:Actins / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D065095:Calcineurin Inhibitors; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002448:Cell Adhesion; D006801:Humans; D016023:Integrins / Q000378:metabolism; D018613:Microscopy, Confocal; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
D000199:Actins; D000906:Antibodies; D018845:CD11 Antigens; D018821:CD18 Antigens; D017252:CD3 Complex; D065095:Calcineurin Inhibitors; D002147:Calmodulin; D016023:Integrins; D015240:Phorbol 12,13-Dibutyrate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase