1995 Fiscal Year Final Research Report Summary
Study of signaling pathways mediated by tyrosine phosphorylation and regulate cadherin-dependent cell adhesion and cytoskeletal organization
| Project/Area Number |
05454168
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
HAMABUCHI Michinari NAGOYA University, Shool of Medicine, Professor, 医学部, 教授 (90135351)
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| Project Period (FY) |
1993 – 1995
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| Keywords | tyrosine phosphorylation / cell adhesion / cytoskeletal structure / MMP-2 / src |
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| Research Abstract |
This project was aimed to study signaling pathways activated by tyrosine phosphorylation and critical for the regulation of cell-cell adhesion and cytoskeletal organization. Tyrosine kinases were originally identifued as a product of oncogenes. However, later studies revealed that tyrosine kinases are also responsible for a wide variety of biological responce such as growth and differentiation of cells, immune responce and platelet aggregation. Despite it importance, precice biochemical precesses required for these responces remain largely unclear. To obtain a clue, we have developed a specific serum that recognize phosphotyrosine residue, and studied growth stimulation and cytoskeletal organization of transformed cells.
In this study, we showed direct evidence that transformation by src activates MMP-2 which catalyzes degradation of extracellular matrix. We found that activation of MMP-2 directly correlates with transforming activity of src and can be inhibited by IFN treatment of cells. We also found that heavy metals can activate c-Src kinase and activated Src forms giant protein complex with other tyrosine phosphorylated proteines that associates with cytoskeletal structure.
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