Interaction between urokinase receptor and heat shock protein MRJ enhances cell adhesion
Copyright policy )Interaction between urokinase receptor and heat shock protein MRJ enhances cell adhesion
The urokinase-type plasminogen activator receptor (uPAR) has diverse biological functions including roles in proteolysis, cell adhesion and cellular signaling. We identified a heat shock protein MRJ (DNAJB6) as a novel uPAR-interacting protein in a yeast two-hybrid screen and confirmed the interaction and co-localization by GST-pull down assays, and co-immunoprecipitation in cells transfected with MRJ. Endogenous interaction between uPAR and MRJ was also detected in breast cancer MDA-MB-231 cells. Deletion mapping demonstrated that the C-terminal region of MRJ is required to mediate its interaction with uPAR. To understand the biological function of the uPAR-MRJ complex, we determined whether MRJ regulated uPAR mediated adhesion to vitronectin in human embryonic kidney (HEK) 293 cells stably transfected with uPAR. After transfection with full length MRJ, there was a 50% increase in cell adhesion compared to the mock transfected control (p<0.01). This increase in adhesion is dependent on the uPAR/full length MRJ interaction as cells transfected with the mutant construct containing only N-terminal region or C-terminal region of MRJ had no increase in cell adhesion. The observed increase in adhesion to vitronectin by MRJ was also blocked by an anti-uPAR domain I antibody suggesting that the induced adhesion is at least in part contributed by uPAR on the cell surface. These data provide a novel mechanism by which uPAR plays a role in cell adhesion to vitronectin.
- University of Newcastle Australia Australia
- UNSW Sydney Australia
- QIMR Berghofer Medical Research Institute Australia
570, Protein Structure, human embryonic kidney cells, anzsrc-for: 3211 Oncology and carcinogenesis, 610, 32 Biomedical and Clinical Sciences, Breast Neoplasms, Nerve Tissue Proteins, 3101 Biochemistry and Cell Biology, Models, Biological, anzsrc-for: 110323 Surgery, Cell Line, Receptors, Urokinase Plasminogen Activator, anzsrc-for: 32 Biomedical and Clinical Sciences, Models, Cell Line, Tumor, Two-Hybrid System Techniques, Breast Cancer, Receptors, 616, Cell Adhesion, 2.1 Biological and endogenous factors, Humans, Vitronectin, anzsrc-for: 31 Biological Sciences, Cancer, Glutathione Transferase, Neoplastic, Tumor, anzsrc-for: 3101 Biochemistry and Cell Biology, anzsrc-for: 1112 Oncology and Carcinogenesis, HSP40 Heat-Shock Proteins, Biological, Protein Structure, Tertiary, Gene Expression Regulation, Neoplastic, urokinase-type plasminogen activator receptor, Gene Expression Regulation, Urokinase Plasminogen Activator, heat shock proteins, Mutation, MRJ interaction, Women's Health, Tertiary, 31 Biological Sciences, Biotechnology, Molecular Chaperones, Signal Transduction
570, Protein Structure, human embryonic kidney cells, anzsrc-for: 3211 Oncology and carcinogenesis, 610, 32 Biomedical and Clinical Sciences, Breast Neoplasms, Nerve Tissue Proteins, 3101 Biochemistry and Cell Biology, Models, Biological, anzsrc-for: 110323 Surgery, Cell Line, Receptors, Urokinase Plasminogen Activator, anzsrc-for: 32 Biomedical and Clinical Sciences, Models, Cell Line, Tumor, Two-Hybrid System Techniques, Breast Cancer, Receptors, 616, Cell Adhesion, 2.1 Biological and endogenous factors, Humans, Vitronectin, anzsrc-for: 31 Biological Sciences, Cancer, Glutathione Transferase, Neoplastic, Tumor, anzsrc-for: 3101 Biochemistry and Cell Biology, anzsrc-for: 1112 Oncology and Carcinogenesis, HSP40 Heat-Shock Proteins, Biological, Protein Structure, Tertiary, Gene Expression Regulation, Neoplastic, urokinase-type plasminogen activator receptor, Gene Expression Regulation, Urokinase Plasminogen Activator, heat shock proteins, Mutation, MRJ interaction, Women's Health, Tertiary, 31 Biological Sciences, Biotechnology, Molecular Chaperones, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).20 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!