The regulation of anoikis: MEKK-1 activation requires cleavage by caspases

Details

Serval ID
serval:BIB_0ABD319BC5BE
Type
Article: article from journal or magazin.
Collection
Publications
Title
The regulation of anoikis: MEKK-1 activation requires cleavage by caspases
Journal
Cell
Author(s)
Cardone  M. H., Salvesen  G. S., Widmann  C., Johnson  G., Frisch  S. M.
ISSN
0092-8674 (Print)
Publication state
Published
Issued date
07/1997
Volume
90
Number
2
Pages
315-23
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jul 25
Abstract
Certain cell types undergo apoptosis when they lose integrin-mediated contacts with the extracellular matrix ("anoikis"). The Jun N-terminal kinase (JNK) pathway is activated in and promotes anoikis. This activation requires caspase activity. We presently report that a DEVD motif-specific caspase that cleaves MEKK-1 specifically is activated when cells lose matrix contact. This cleavage is required for the activation of the kinase activity. When overexpressed, the MEKK-1 cleavage product stimulates apoptosis; the wild-type, full-length MEKK-1 sensitizes cells to anoikis; and a cleavage-resistant mutant of MEKK-1 partially protects cells against anoikis. The cleavage-resistant or kinase-inactive mutants also prevent caspase-7 from being activated completely. Thus, caspases can induce apoptosis by activating MEKK-1, which in turn activates more caspase activity, comprising a positive feedback loop.
Keywords
Amino Acid Sequence Animals Apoptosis/drug effects/*physiology Caspase 7 *Caspases Cells, Cultured Cysteine Endopeptidases/isolation & purification/*metabolism Dogs Enzyme Activation Kidney Tubules, Distal/cytology Molecular Sequence Data Protein Structure, Tertiary Protein-Serine-Threonine Kinases/antagonists & inhibitors/chemistry/*metabolism Serpins/pharmacology Transfection *Viral Proteins
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:43
Last modification date
20/08/2019 12:32
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