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.
Fagerholm, S. C., Prescott, A., Cohen, P., Gahmberg, C. G., & Lehto, V-P. (Ed.) (2001). An essential role for calmodulin in regulating human T cell aggregation. FEBS Letters, 491(1-2), 131-6. https://doi.org/10.1016/S0014-5793(01)02182-2