Document Detail

DAPK-1 binding to a linear peptide motif in MAP1B stimulates autophagy and membrane blebbing.
MedLine Citation:
PMID:  18195017     Owner:  NLM     Status:  MEDLINE    
DAPK-1 (death-activated protein kinase) has wide ranging functions in cell growth control; however, DAPK-1 interacting proteins that mediate these effects are not well defined. Protein-protein interactions are driven in part by linear interaction motifs, and combinatorial peptide libraries were used to identify peptide interfaces for the kinase domain of DAPK-1. Peptides bound to DAPK-1core kinase domain fragments had homology to the N-terminal domain of the microtubule-associated protein MAP1B. Immunobinding assays demonstrated that DAPK-1 can bind to the full-length human MAP1B, a smaller N-terminal miniprotein containing amino acids 1-126 and the 12-amino acid polypeptides acquired by peptide selection. Amino acid starvation of cells induced a stable immune complex between MAP1B and DAPK-1, identifying a signal that forms the endogenous complex in cells. DAPK-1 and MAP1B co-expression form a synthetic lethal interaction as they cooperate to induce growth inhibition in a clonogenic assay. In cells, two co-localizing populations of DAPK-1 and MAP1B were observed using confocal microscopy; one pool co-localized with MAP1B plus tubulin, and a second pool co-localized with MAP1B plus cortical F-actin. Reduction of MAP1B protein using short interfering RNA attenuated DAPK-1-stimulated autophagy. Transfected MAP1B can synergize with DAPK-1 to stimulate membrane blebbing, whereas reduction of MAP1B using short interfering RNA attenuates DAPK-1 membrane blebbing activity. The autophagy inhibitor 3-methyladenine inhibits the DAPK-1 plus MAP1B-mediated membrane blebbing. These data highlight the utility of peptide aptamers to identify novel binding interfaces and highlight a role for MAP1B in DAPK-1-dependent signaling in autophagy and membrane blebbing.
Ben Harrison; Michaela Kraus; Lindsay Burch; Craig Stevens; Ashley Craig; Phillip Gordon-Weeks; Ted R Hupp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-08     Completed Date:  2008-05-28     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9999-10014     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/NM004938;  NM005909
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MeSH Terms
Actins / genetics,  metabolism
Adenine / analogs & derivatives,  pharmacology
Amino Acid Motifs / physiology
Apoptosis Regulatory Proteins / antagonists & inhibitors,  genetics,  metabolism*
Autophagy / drug effects,  physiology*
Base Sequence
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors,  genetics,  metabolism*
Cell Line
Cell Membrane / genetics,  metabolism*
Death-Associated Protein Kinases
Microtubule-Associated Proteins / genetics,  metabolism*
Molecular Sequence Data
Nerve Tissue Proteins / genetics,  metabolism*
Peptide Library
Peptides / genetics,  metabolism
Protein Binding / physiology
Signal Transduction / drug effects,  physiology*
Tubulin / genetics,  metabolism
Grant Support
G0400034//Medical Research Council; G9900989//Medical Research Council; //Cancer Research UK; //Medical Research Council
Reg. No./Substance:
0/Actins; 0/Apoptosis Regulatory Proteins; 0/MAP1B protein, human; 0/Microtubule-Associated Proteins; 0/Nerve Tissue Proteins; 0/Peptide Library; 0/Peptides; 0/Tubulin; 5142-23-4/3-methyladenine; EC protein, human; EC Protein Kinases; EC Protein Kinases; JAC85A2161/Adenine

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