The TryPIKinome of five human pathogenic trypanosomatids: Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania infantum--new tools for designing specific inhibitors.
Phosphatidylinositol (PI) kinases are at the heart of one of the major pathways of intracellular signal transduction. Herein, we present the first report on a survey made by similarity searches against the five human pathogenic trypanosomatids Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania infantum genomes available to date for phosphatidylinositol- and related-kinases (TryPIKs). In addition to generating a panel called "The TryPIKinome", we propose a model of signaling pathways for these TryPIKs. The involvement of TryPIKs in fundamental pathways, such as intracellular signal transduction and host invasion processes, makes the study of TryPIKs an important area for further inquiry. New subtype-specific inhibitors are expected to work on individual members of the PIK family and, therefore, can presumably neutralize trypanosomatid invasion processes.
Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil. dianabahia@hotmail.com
Diana
D
Bahia
Luciana Márcia
LM
Oliveira
Fabio Mitsuo
FM
Lima
Priscila
P
Oliveira
José Franco da
JF
Silveira
Renato Arruda
RA
Mortara
Jerônimo Conceição
JC
Ruiz
D019870:1-Phosphatidylinositol 4-Kinase / Q000037:antagonists & inhibitors / Q000145:classification* / Q000235:genetics; D000595:Amino Acid Sequence; D000730:Androstadienes / Q000737:chemistry / Q000494:pharmacology; D001343:Autophagy; D002462:Cell Membrane / Q000201:enzymology; D048749:Cytokinesis / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007892:Leishmania braziliensis / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D018314:Leishmania infantum / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D018320:Leishmania major / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D008239:Lysine / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D014351:Trypanosomatina / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D014344:Trypanocidal Agents; D019870:1-Phosphatidylinositol 4-Kinase; D008239:Lysine; D000077191:Wortmannin