Linked Life Data

17148436

Source:http://linkedlifedata.com/resource/pubmed/id/17148436

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-1-29
pubmed:abstractText
The Bordetella adenylate cyclase toxin-hemolysin (CyaA) targets phagocytes expressing the alpha(M)beta2 integrin (CD11b/CD18), permeabilizes their membranes by forming small cation-selective pores, and delivers into cells a calmodulin-activated adenylate cyclase (AC) enzyme that dissipates cytosolic ATP into cAMP. We describe here a third activity of CyaA that yields elevation of cytosolic calcium concentration ([Ca2+]i) in target cells. The CyaA-mediated [Ca2+]i increase in CD11b+ J774A.1 monocytes was inhibited by extracellular La3+ ions but not by nifedipine, SK&F 96365, flunarizine, 2-aminoethyl diphenylborinate, or thapsigargin, suggesting that influx of Ca2+ into cells was not because of receptor signaling or opening of conventional calcium channels by cAMP. Compared with intact CyaA, a CyaA-AC- toxoid unable to generate cAMP promoted a faster, albeit transient, elevation of [Ca2+]i. This was not because of cell permeabilization by the CyaA hemolysin pores, because a mutant exhibiting a strongly enhanced pore-forming activity (CyaA-E509K/E516K), but unable to deliver the AC domain into cells, was also unable to elicit a [Ca2+]i increase. Further mutations interfering with AC translocation into cells, such as proline substitutions of glutamate residues 509 or 570 or deletion of the AC domain as such, reduced or ablated the [Ca2+]i-elevating capacity of CyaA. Moreover, structural alterations within the AC domain, because of insertion of various oligopeptides, differently modulated the kinetics and extent of Ca2+ influx elicited by the respective AC- toxoids. Hence, the translocating AC polypeptide itself appears to participate in formation of a novel type of membrane path for calcium ions, contributing to action of CyaA in an unexpected manner.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2808-20
pubmed:meshHeading
pubmed-meshheading:17148436-Adenosine Triphosphate, pubmed-meshheading:17148436-Adenylate Cyclase, pubmed-meshheading:17148436-Adenylate Cyclase Toxin, pubmed-meshheading:17148436-Amino Acid Substitution, pubmed-meshheading:17148436-Animals, pubmed-meshheading:17148436-Antigens, CD11b, pubmed-meshheading:17148436-Biological Transport, pubmed-meshheading:17148436-Calcium, pubmed-meshheading:17148436-Catalysis, pubmed-meshheading:17148436-Cell Line, pubmed-meshheading:17148436-Cell Membrane, pubmed-meshheading:17148436-Cyclic AMP, pubmed-meshheading:17148436-Hemolysis, pubmed-meshheading:17148436-Macrophages, pubmed-meshheading:17148436-Mice, pubmed-meshheading:17148436-Monocytes, pubmed-meshheading:17148436-Mutagenesis, Site-Directed, pubmed-meshheading:17148436-Polymerase Chain Reaction, pubmed-meshheading:17148436-Recombinant Proteins, pubmed-meshheading:17148436-Sheep
pubmed:year
2007
pubmed:articleTitle
Third activity of Bordetella adenylate cyclase (AC) toxin-hemolysin. Membrane translocation of AC domain polypeptide promotes calcium influx into CD11b+ monocytes independently of the catalytic and hemolytic activities.
pubmed:affiliation
Department of Genetics and Microbiology, Faculty of Science, Charles University, CZ-128 44, Prague 2.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't