INTERFERON-GAMMA ACTIVATION OF A MITOGEN-ACTIVATED PROTEIN-KINASE, KFR1, IN THE BLOOD-STREAM FORM OF TRYPANOSOMA-BRUCEI

KFR1, a mitogen-activated protein (MAP) kinase identified in the Afric an trypanosome, Trypanosoma brucei, is a serine protein kinase capable of phosphorylating the serine residues in histone H-1, myelin basic p rotein, and beta-casein. It phosphorylates four proteins with estimate d molecular masses of 22, 54, 46, and 90 kDa from the T. brucei bloods tream-form lysate in vitro. KFR1 bears significant sequence similarity to the yeast MAP kinases KSS1 and FUS3 but cannot functionally comple ment the Kss1/fus3 yeast mutant. It is encoded by a single-copy gene i n the diploid T. brucei, and only one of the two alleles can be succes sfully disrupted, suggesting an essential function of KFR1 in T. bruce i. KFR1 activity is present at a much enhanced level in the bloodstrea m form of T. brucei when compared with that in the insect (procyclic) form. This enhanced activity can be eliminated in vitro by the treatme nt with protein phosphatase HVH2 known to act specifically on MAP kina ses. It can also be decreased in the bloodstream form of T. brucei by serum starvation but induced specifically by interferon-gamma. The pro duction of interferon-gamma in the mammalian host is known to be trigg ered by T. brucei infection, and this cytokine, as has been reported, promotes the proliferation of T. brucei in the mammalian blood. Since none of these phenomena can be observed in the procyclic form of T. br ucei, activation of KFR1 is most likely involved in mediating the inte rferon-gamma-induced proliferation of T. brucei in the mammalian host.