Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes.
We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both ... proteins. Phosphorylation of BimL by Pak1 prevents it from interacting with and inactivation of Bcl-2, an antiapoptotic protein. Overexpression of DLC1 but not DLC1-Ser88Ala mutant promotes cancerous properties of breast cancer cells. DLC1 protein level is elevated in more than 90% of human breast tumors. The regulation of cell survival functions by Pak1-DLC1 interaction represents a novel mechanism by which a signaling kinase might regulate the cancerous phenotypes.
Mesh Terms:
Alanine, Apoptosis, Blotting, Western, Breast Neoplasms, Carrier Proteins, Cell Cycle, Cell Division, Cell Line, Tumor, Cell Survival, Cell Transformation, Neoplastic, Drosophila Proteins, Dyneins, Flow Cytometry, Gene Expression Regulation, Neoplastic, Glutathione Transferase, Humans, Immunohistochemistry, Microscopy, Fluorescence, Mutation, Neoplasms, Phenotype, Phosphorylation, Plasmids, Protein Binding, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Serine, Signal Transduction, Time Factors, Two-Hybrid System Techniques, Up-Regulation, p21-Activated Kinases
Alanine, Apoptosis, Blotting, Western, Breast Neoplasms, Carrier Proteins, Cell Cycle, Cell Division, Cell Line, Tumor, Cell Survival, Cell Transformation, Neoplastic, Drosophila Proteins, Dyneins, Flow Cytometry, Gene Expression Regulation, Neoplastic, Glutathione Transferase, Humans, Immunohistochemistry, Microscopy, Fluorescence, Mutation, Neoplasms, Phenotype, Phosphorylation, Plasmids, Protein Binding, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Serine, Signal Transduction, Time Factors, Two-Hybrid System Techniques, Up-Regulation, p21-Activated Kinases
Cancer Cell
Date: Jun. 01, 2004
PubMed ID: 15193260
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