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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Candas, Mehmet Griko, Natalya B. Bulla, Lee A. Taussig, Ronald Zhang, Xuebin |
| Description | Author Affiliation: Zhang X ( Biological Targets Inc., Dallas, TX 75235, USA.); |
| Abstract | Many pathogenic organisms and their toxins target host cell receptors, the consequence of which is altered signaling events that lead to aberrant activity or cell death. A significant body of literature describes various molecular and cellular aspects of toxins associated with bacterial invasion, colonization, and host cell disruption. However, there is little information on the molecular and cellular mechanisms associated with the insecticidal action of Bacillus thuringiensis (Bt) Cry toxins. Recently, we reported that the Cry1Ab toxin produced by Bt kills insect cells by activating a Mg(2+)-dependent cytotoxic event upon binding of the toxin to its receptor BT-R(1). Here we show that binding of Cry toxin to BT-R(1) provokes cell death by activating a previously undescribed signaling pathway involving stimulation of G protein (G(alphas)) and adenylyl cyclase, increased cAMP levels, and activation of protein kinase A. Induction of the adenylyl cyclase/protein kinase A pathway is manifested by sequential cytological changes that include membrane blebbing, appearance of ghost nuclei, cell swelling, and lysis. The discovery of a toxin-induced cell death pathway specifically linked to BT-R(1) in insect cells should provide insights into how insects evolve resistance to Bt and into the development of new, safer insecticides. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 26 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adenylate Cyclase Metabolism Bacterial Proteins Toxicity Bacterial Toxins Cyclic AMP-Dependent Protein Kinases Endotoxins Insect Proteins Agonists Lepidoptera Drug Effects Receptors, Cell Surface Adenylyl Cyclase Inhibitors Animals Apoptosis Cell Death Cells, Cultured Cyclic AMP Antagonists & Inhibitors Endocytosis Enzyme Inhibitors Pharmacology GTP-Binding Proteins Hemolysin Proteins Cytology Enzymology Signal Transduction Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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