التفاصيل البيبلوغرافية
| العنوان: |
A ß1 integrin signaling pathway involving Src-family kinases, Cbl and PI-3 kinase is required for macrophage spreading and migration. |
| المؤلفون: |
Fanying Meng1, Lowell, Clifford A.1 clowell@cgl.ucsf.edu |
| المصدر: |
EMBO Journal. 8/1/98, Vol. 17 Issue 15, p4391-4403. 13p. |
| مصطلحات موضوعية: |
*MACROPHAGES, *INTEGRINS, *PROTEINS, *AMINO acids, *FIBRONECTINS, *OLIGONUCLEOTIDES, *CELLULAR signal transduction |
| مستخلص: |
We have used mutant macrophages which are deficient in expression of Src-family kinases to define an integrin signaling pathway that is required for macro- phage adhesion and migration. Following ligation of surface integrins by fibronectin, the p120 c-cbl (Cbl) protein rapidly becomes tyrosine phosphorylated and associated with the Src-family kinases Fgr and Lyn. In hck/fgr/lyn/ triple mutant cells, which are defective in spreading on fibronectin-coated surfaces in vitro and show impaired migration in vivo, Cbl tyrosine phosphorylation is blocked, Cbl protein levels are low, adhesion-dependent translocation of Cbl to the membrane is impaired and Cbl-associated, membrane-localized phosphatidylinositol 3 (PI-3)-kinase activity is dramatically reduced. In contrast, adhesion-dependent activation of total cellular PI-3 kinase activity is normal in mutant cells, demonstrating that it is the membrane-associated fraction of PI-3 kinase which is most critical in regulating actin cytoskeletal rearrangements that lead to cell spreading. Treatment of wild-type cells with the Src-family-specific inhibitor PP1, Cbl antisense oligonucleotides or pharmacological inhibitors of PI-3 kinase blocks cell spreading on fibronectin surfaces. These data provide a molecular description for the role of Src-family kinases Hck, Fgr and Lyn in β1-integrin signal transduction in macrophages. [ABSTRACT FROM AUTHOR] |
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