Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation.
Adhesion to extracellular matrix mediates cell cycle progression in mid-late G1; this effect involves an integrin-dependent organization of the cytoskeleton and a consequent change in cell shape. In an effort to identify potential signal-transducing agents that are associated with integrin-dependent shape changes, we looked for kinase activities that were stimulated by long-term adhesion of G0-synchronized NIH-3T3 cells to fibronectin-coated dishes. Several kinase activities were stimulated by this procedure, two of which migrated at 42 and 44 kDa and phosphorylated myelin basic protein in vitro. Blotting with anti-phosphotyrosine and anti-mitogen-activated protein (MAP) kinase antibodies identified these enzymes as ERK 1 and ERK 2. In contrast to the rapid and transient activation of these MAP kinases by platelet-derived growth factor, stimulation of MAP kinase activity by fibronectin was gradual, persistent, and associated with cell spreading rather than cell attachment itself. Cytochalasin D blocked the activation of MAP kinase activity that was induced by the binding of cells to fibronectin. Moreover, MAP kinase was also activated by adhesion of cells to vitronectin and type IV collagen; these effects were also associated with cell spreading. These results distinguish the regulation of G1 phase MAP kinase activity by soluble mitogens and extracellular matrix. They also implicate MAP kinase in shape-dependent cell cycle progression.
Zhu
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Department of Cell Biology and Anatomy, University of Miami School of Medicine, Florida 33101, USA.
Assoian
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D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002448:Cell Adhesion; D002455:Cell Division; D015638:Cytochalasin D / Q000494:pharmacology; D004789:Enzyme Activation; D005353:Fibronectins / Q000494:pharmacology; D016023:Integrins / Q000502:physiology*; D007399:Interphase; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D005353:Fibronectins; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D015638:Cytochalasin D; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases