A model of MEK-ERK signaling in TGF-β1-dependent control of <i>P. falciparum</i> development.

<p>Human TGF-β1 ingested during the blood meal activates MEK-ERK signaling in mosquito cells. Activation of ERK inhibits <i>NOS</i> gene expression which reduces nitric oxide synthase levels and the synthesis of reactive oxygen and nitrogen species. MEK-ERK signaling may inhibit the expression of other anti-parasite genes as well that function together with <i>NOS</i> to limit parasite development. Inhibition of the expression of <i>NOS</i> and other anti-parasite gene products would favor <i>P. falciparum</i> development in the mosquito midgut. In contrast, inhibition of MEK-ERK signaling by the MEK inhibitors PD98059 or U0126 increases anti-parasite activity, including TGF-β1-dependent <i>NOS</i> gene expression. Increased <i>NOS</i> expression results in higher nitric oxide synthase enzyme levels and the generation of inflammatory levels of reactive oxygen and nitrogen species <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000366#ppat.1000366-Peterson1" target="_blank">[7]</a> that are toxic to the parasite.