Anthrax edema factor potency depends on mode of cell entry.
Anthrax edema factor (EF) is a highly active calmodulin-dependent adenylyl cyclase toxin that can potently raise intracellular cAMP levels causing a broad range of tissue damage. EF needs anthrax protective antigen (PA) to enter into the host cell and together they form edema toxin. Here, we examine factors that are critical for edema toxin cell entry and potency. In Y1, 293T and mouse embryonic fibroblast cells, EF causes cell rounding, aggregation, and sometimes detachment via protein kinase A but not Epac. The rate-limiting step for these EF-mediated effects is cellular entry via the anthrax toxin receptor. Finally, EF potency is also enhanced if the EF adenylyl cyclase domain is transfected into host cells, even in the absence of the anthrax PA-binding domain. These results indicate that the effects of EF in cells can differ dependent upon the mode of cellular entry of the adenylyl cyclase.
Hong
Jia
J
Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
Beeler
Jeff
J
Zhukovskaya
Natalia L
NL
He
Weisong
W
Tang
Wei-Jen
WJ
Rosner
Marsha Rich
MR
D000262:Adenylyl Cyclases / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001483:Base Sequence; D020134:Catalytic Domain; D002459:Cell Fusion; D002460:Cell Line; D048430:Cell Shape; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D051379:Mice; D014162:Transfection
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D017931:DNA Primers; C482601:Epac protein, mouse; D020662:Guanine Nucleotide Exchange Factors; C030325:anthrax toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases