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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Halenbeck, R. Roulston, A. Lee, N. Williams, L. T. Macdonald, H. Shi, T. Reinhard, C. |
| Description | Author Affiliation: Lee N ( Chiron Technologies, Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.); |
| Abstract | Apoptosis is a highly regulated form of cell death, characterized by distinctive features such as cellular shrinkage and nuclear condensation. We demonstrate here that proteolytic activation of hPAK65, a p21-activated kinase, induces morphological changes and elicits apoptosis. hPAK65 is cleaved both in vitro and in vivo by caspases at a single site between the N-terminal regulatory p21-binding domain and the C-terminal kinase domain. The C-terminal cleavage product becomes activated, with a kinetic profile that parallels caspase activation during apoptosis. This C-terminal hPAK65 fragment also activates the c-Jun N-terminal kinase pathway in vivo. Microinjection or transfection of this truncated hPAK65 causes striking alterations in cellular and nuclear morphology, which subsequently promotes apoptosis in both CHO and Hela cells. Conversely, apoptosis is delayed in cells expressing a dominant-negative form of hPAK65. These findings provide a direct evidence that the activated form of hPAK65 generated by caspase cleavage is a proapoptotic effector that mediates morphological and biochemical changes seen in apoptosis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 25 |
| Volume Number | 94 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1997-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Physiology Caspases Cysteine Endopeptidases Metabolism Mitogen-Activated Protein Kinases Ribosomal Protein S6 Kinases Animals CHO Cells Calcium-Calmodulin-Dependent Protein Kinases Genetics Caspase 3 Cell Line Cricetinae Enzyme Activation HeLa Cells JNK Mitogen-Activated Protein Kinases Mice Sequence Deletion Substrate Specificity Transfection Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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