Abstract
In various vascular diseases, extracellular matrix (ECM) and integrin expression are frequently altered, leading to focal adhesion kinase (FAK) or proline-rich tyrosine kinase 2 (Pyk2) activation. In addition to the major roles of FAK and Pyk2 in regulating adhesion dynamics via integrins, recent studies have shown a new role for nuclear FAK in gene regulation in various vascular cells. In particular, FAK primarily localizes within the nuclei of vascular smooth muscle cells (VSMCs) of healthy arteries. However, vessel injury increased FAK localization back to adhesions and elevated FAK activity, leading to VSMC hyperplasia. The study suggested that abnormal FAK or Pyk2 activation in vascular cells may cause pathology in vascular diseases. Here we will review several studies of FAK and Pyk2 associated with integrin signaling in vascular diseases including restenosis, atherosclerosis, heart failure, pulmonary arterial hypertension, aneurysm, and thrombosis. Despite the importance of FAK family kinases in vascular diseases, comprehensive reviews are scarce. Therefore, we summarized animal models involving FAK family kinases in vascular diseases.
Highlights
Cell–matrix adhesion plays a significant role in maintaining normal tissue structure and in promoting pathological remodeling in many human diseases [1]
It will need further testing, it is plausible that the high levels of FAK-related nonkinase (FRNK) found in vascular smooth muscle cells (VSMCs) may contribute to the increased nuclear focal adhesion kinase (FAK) and inactive FAK that we observed within VSMCs of healthy arteries
We have discussed the close association between FAK family kinases and integrin signaling in vascular diseases
Summary
Cell–matrix adhesion plays a significant role in maintaining normal tissue structure and in promoting pathological remodeling in many human diseases [1]. The ECM–integrin interaction plays an important role in promoting cell attachment, and in facilitating signaling of other cell surface receptors such as growth factors, cytokines, and G-protein-coupled receptors (Figure 2) (reviewed in [10,11]). Signaling through these receptors is often dependent on integrin occupancy as lack of cell attachment has been. While the role of FAK family signaling in regulating focal adhesion dynamics via integrins or in further transmitting other surface receptor signaling has been extensively studied, it has been shown that FAK can localize to the nucleus and plays a key role in regulating gene expression by modulating transcription factor stability [14,15,16]. We discuss the role of FAK and Pyk in various vascular diseases
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