Specific Phosphorylations Transmit Signals from Leukocyte {beta}2- to {beta}1-Integrins and Regulate Adhesion [Cell Biology]

October 2nd, 2014 by Uotila, L. M., Jahan, F., Soto Hinoȷosa, L., Melandri, E., Gronholm, M., Gahmberg, C. G.

The regulation of integrins expressed on leukocytes must be precisely controlled, and members of different integrin subfamilies have to act in concert to ensure proper traffic of immune cells to sites of inflammation. The activation of β2 family integrins through the T cell receptor or by chemokines leads to the inactivation of very late antigen-4. The mechanism(s) of this crosstalk has not been known. We have now elucidated in detail how the signals are transmitted from leukocyte-function associated antigen-1 and show that, after its activation, the signaling involves specific phosphorylations of the β2-integrin followed by interactions with cytoplasmic signaling proteins. This results in loss of β1 phosphorylation and a decrease in very late antigen-4 binding to its ligand vascular cell adhesion molecule-1. Our results show how a member of one integrin family regulates the activity of another integrin. This is important for the understanding of integrin-mediated processes.