FAK is a critical signalling component associated with areas of substratum adhesion; signalling via FAK is mediated through autophosphorylation of Tyr 397 [51] . We demonstrate that sACE2, at levels comparable to those reported in human plasma, significantly reduces FAK phosphorylation levels. Furthermore, we show that treatment with sACE2 increases the levels of Akt expression, a pro-survival, pro-proliferative protein. Changes in the level of phosphorylated Akt were also seen in response to sACE2; however, these were accounted for by the increase in the amount of total Akt. As such, signalling by Akt was not transmitted to its downstream effector NF-kB. sACE2 has no known function. We do not dismiss the possibility that this circulating ACE2 may bind integrins, when released from the plasma membrane, and elicit autocrine or paracrine signalling. In fact, one of the shed forms of the amyloid precursor protein, sAPPa, binds to ITGB1 and signals to enhance axon outgrowth [52] . What is more, cellular expression of full length APP inhibits axonal outgrowth and an excess of the shed form overcomes this inhibition [52] . We therefore propose some of the anti-proliferative actions of ACE2 may in part be mediated through a non-catalytic interaction with integrins, rather than by metabolism of Ang II per se. These data suggest that ACE2, through its integrin binding abilities, may have regulatory roles in cellular attachment and support a novel mechanism of integrin activation upon ACE2 shedding.