Model for cooperativity between PfCDPK5 and PfPKG. The progress along the parasite egress pathway is promoted by activation of PfPKG. At low levels of PfPKG activation, the protease cascade and calcium signaling pathway are initiated. PfCDPK5 activation, together with PfPKG, leads to further progression of the protease cascade and triggered release of micronemes required for parasite egress (detected by PfAMA1 translocation, shown in red). Under physiological conditions, this step requires both PfCDPK5 and PfPKG. The discharge of micronemes completes the egress process with the release of invasive merozoites. The requirement for PfCDPK5 can be bypassed by supraphysiological activation of PfPKG by either BIPPO or physical disruption. PVM, parasitophorous vacuolar membrane.