ENV59-GP3 Immune Suppression via Inhibition of the Intermediate
Conductance Calcium Activated Potassium Channel KCa3.1
Despite the extensive literature documenting a broad range of immune
suppressive activity affecting different signal transduction pathways by
retroviral derived immune suppressive peptides, no precise molecular
mechanism of action (MoA) has been described. ENV59-GP3 is derived from
an endogenous retroviral envelope protein and thus is expressed on the
surface of immune cells. Therefore, it can be expected that it will
interact with a surface receptor. We noted that KCa3.1
is a surface protein and that inhibition of KCa3.1
protected mice from developing severe colitis in two mouse models
of inflammatory bowel disease [11], furthermore
KCa3.1 inhibitor ameliorate the disease progression in
EAE mice [19]. The overlap between the activity of
KCa3.1 and our observations of the ENV59 activity made
it a good candidate for further investigation.