| Autor: |
Relou IA; Laboratory for Thrombosis and Haemostasis, Department of Haematology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. i.relou@azu.nl, Bax LA, van Rijn HJ, Akkerman JW |
| Jazyk: |
angličtina |
| Zdroj: |
The Biochemical journal [Biochem J] 2003 Jan 15; Vol. 369 (Pt 2), pp. 407-16. |
| DOI: |
10.1042/BJ20020410 |
| Abstrakt: |
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase implicated in signalling pathways mediated by integrins and G-protein-coupled receptors (GPCRs). Upon stimulation FAK is phosphorylated on six tyrosine residues. Here we report the site-specific phosphorylation by low-density lipoprotein (LDL), which is known to induce integrin-independent FAK phosphorylation, and compare this with the effect of thrombin, which phosphorylates FAK via integrin alphaIIbbeta3. Stimulation with LDL reveals (i) a major role for Tyr-925 phosphorylation which surpasses the phosphorylation of the other residues, including Tyr-397, in rate and extent, (ii) alphaIIbbeta3-independent phosphorylation of Tyr-925 and Tyr-397, and (iii) complex formation between FAK and the Src-kinase Fgr but not with c-Src. These patterns differ profoundly from those induced by thrombin. LDL-induced phosphorylation of Tyr-925 and Tyr-397 was inhibited by 60-75% by receptor-associated protein, an inhibitor of members of the LDL receptor family. Thus these findings reveal a novel mechanism of FAK phosphorylation by signalling cascades involving a member of the LDL receptor family. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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