Serine 756 of β2 integrin controls Rap1 activity during inside-out activation of αMβ2

Jenson Lim (1) , Neil A Hotchin , Emmanuelle Caron

1 Division of Cell & Molecular Biology

During αMβ2-mediated phagocytosis, the small GTPase Rap1 activates the β2 integrin by binding to a region between residues 732 - 761. Using COS-7 cells transfected with αMβ2, we show that αMβ2 activation by the phorbol ester, PMA, involves serine residue 756 of β2. This residue is critical for the local positioning of talin, and biochemically interacts with Rap1. Using the calmodulin antagonist W7, we found Rap1 recruitment and inside-out activation of αMβ2 to be affected. We also report a role for calcium/calmodulin kinase II (CamKII) in the activation of Rap1 during integrin activation. These results demonstrate a distinct, physiological role for the serine residue 756 of β2 integrin, in conjunction with the actions of talin and Rap1, during αMβ2 activation in macrophages.

Mots clés: Life Sciences

Jenson Lim, Neil A Hotchin, Emmanuelle Caron. Serine 756 of β2 integrin controls Rap1 activity during inside-out activation of αMβ2. Biochemical Journal, 2011, 437 (3), pp.461-467. ⟨10.1042/BJ20101666⟩. ⟨hal-00608391⟩