Site-specific phosphorylation of platelet focal adhesion kinase by low-density lipoprotein.

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.
Mesh Terms:
Blood Platelets, Dose-Response Relationship, Drug, Enzyme Activation, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Humans, LDL-Receptor Related Protein-Associated Protein, Lipoproteins, LDL, Phosphorylation, Platelet Glycoprotein GPIIb-IIIa Complex, Protein-Tyrosine Kinases, Signal Transduction, Thrombin, Tyrosine, src-Family Kinases
Biochem. J.
Date: Jan. 15, 2003
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