Urokinase plasminogen activator receptor, beta 2-integrins, and Src-kinases within a single receptor complex of human monocytes
| Autor: | U H Weidle, Otto Majdic, Johannes Stöckl, Hannes Stockinger, I Bartke, Walter Knapp, J Bohuslav, Vaclav Horejsi, C Hansmann |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Integrins
Receptor complex Macromolecular Substances Immunology Receptor Protein-Tyrosine Kinases Integrin Macrophage-1 Antigen Receptors Cell Surface Biology Proto-Oncogene Proteins c-fyn Monocytes Receptors Urokinase Plasminogen Activator chemistry.chemical_compound Antigens CD Cell Movement Multienzyme Complexes Proto-Oncogene Proteins Cell Adhesion Humans Immunology and Allergy Lymphocyte function-associated antigen 1 Phosphorylation Cell adhesion Tyrosine phosphorylation Articles Protein-Tyrosine Kinases Lymphocyte Function-Associated Antigen-1 Urokinase receptor src-Family Kinases chemistry Biochemistry CD18 Antigens Proto-Oncogene Proteins c-hck biology.protein Signal transduction Protein Processing Post-Translational Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.181.4.1381 |
| Popis: | The glycosylphosphatidylinositol (GPI)-anchored membrane protein urokinase plasminogen activator-receptor (uPA-R; CD87) is one of the key molecules involved in migration of leukocytes and tumor cells. uPA bound to uPA-R provides the cell proteolytic potential used for degradation of extracellular matrix. uPA-R is also involved in induction of cell adhesion and chemotaxis. Here, we provide a molecular explanation for these uPA-R-related cellular events. By size fractionation of monocyte lysate and affinity isolation on its natural ligand uPA, we demonstrate uPA-R as a component of a receptor complex of relatively large size. Reprecipitation and immunoblotting techniques allowed us to detect the protein tyrosine kinases (PTKs) p60fyn, p53/56lyn, p58/64hck, and p59fgr as components of this "uPA-R complex". Activation of monocytes even with enzymatically inactivated uPA resulted in induction of tyrosine phosphorylation, suggesting modulation of uPA-R-associated PTKs upon ligand binding. In spite of their presence in large complexes, we did not find the GPI-linked proteins CD14, CD58, and CD59 in the uPA-R complex, which indicates the presence of different receptor domains containing GPI-linked proteins in monocytes. However, we identified the leukocyte integrins LFA-1 and CR3 as components of the uPA-R complex as indicated by coisolation of these molecules, as well as by cocapping and comodulation of uPA-R and leukocyte integrins on the monocyte surface. The assemblage of uPA-R, PTKs and membrane spanning beta 2-integrins in one receptor complex indicates functional cooperation. In regard to the involvement of these molecules in pericellular proteolysis, signal transduction, as well as adhesion and chemotactic movement, we suggest uPA-R complex as a potential cellular device for cell migration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|