Transforming growth factor alpha binds to Trypanosoma cruzi amastigotes to induce signaling and cellular proliferation.
Macrophages secrete transforming growth factor alpha (TGF-alpha) to trigger proliferation of cancer cells. Here, we report a new role for TGF-alpha in modulating the direct cellular proliferation of a parasitic protozoan, Trypanosoma cruzi. Amastigotes present two classes of receptors for TGF-alpha with different binding affinities. (125)I-TGF-alpha binding was competed by an excess of cold epidermal growth factor and TGF-alpha but not by an irrelevant molecule. Upon binding of TGF-alpha to amastigotes, the ligand is internalized, inducing trypanosome tyrosine phosphorylation of 90- and 87-kDa proteins and increasing DNA synthesis and proliferation of amastigotes. Furthermore, exposure of macrophages to TGF-alpha induced increased amastigote proliferation. These results describe a novel mechanism used by amastigotes to regulate their proliferation mediated by a TGF-alpha-dependent signal transduction pathway.
Alexander
A Deloris
AD
Department of Microbiology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Villalta
Fernando
F
Lima
Maria F
MF
D000818:Animals; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D008264:Macrophages / Q000469:parasitology; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D016211:Transforming Growth Factor alpha / Q000378:metabolism* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D016211:Transforming Growth Factor alpha; D014443:Tyrosine; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors