Endocytosis of Candida albicans by vascular endothelial cells is associated with tyrosine phosphorylation of specific host cell proteins.
Candida albicans escapes from the bloodstream by invading the endothelial cell lining of the vasculature. In vitro, C. albicans invades endothelial cells by inducing its own endocytosis. We examined whether this process is regulated by the tyrosine phosphorylation of endothelial cell proteins. We found that endocytosis of wild-type C. albicans was accompanied by the tyrosine phosphorylation of two endothelial cell proteins with molecular masses of 80 and 82 kDa. The phosphorylation of these proteins was closely associated with the endocytosis of C. albicans because these proteins were phosphorylated in response to the endocytosis of both live and killed organisms, but they were not phosphorylated in endothelial cells infected with a poorly endocytosed strain of C. albicans. The tyrosine kinase inhibitors genistein and tyrphostin 47 blocked the phosphorylation of the two endothelial cell proteins and significantly reduced endocytosis of C. albicans. Therefore, C. albicans probably induces its own endocytosis by stimulating the tyrosine phosphorylation of two endothelial cell proteins.
Belanger
Paul H
PH
St John's Cardiovascular Research Center, Division of Infectious Diseases, Department of Medicine, Harbor-UCLA Research and Education Institute, Torrance, California 90502, USA.
Johnston
Douglas A
DA
Fratti
Rutilio A
RA
Zhang
Mason
M
Filler
Scott G
SG
D001422:Bacterial Adhesion; D002176:Candida albicans / Q000472:pathogenicity*; D002478:Cells, Cultured; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011506:Proteins; D020032:Tyrphostins; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases