Focal adhesion kinase -- the basis of local hypertrophic signaling domains.
ABSTRACT Focal adhesion kinase (FAK), a broadly expressed non-receptor tyrosine kinase which transduces signals from integrins, growth and hormonal factors, is a key player in many fundamental biological processes and functions, including cell adhesion, migration, proliferation and survival. The involvement of FAK in this range of functions supports its role in important aspects of organismal development and disease, such as central nervous system and cardiovascular development, cancer, cardiac hypertrophy and tissue fibrosis. Many functions of FAK are correlated with its tyrosine kinase activity, which is temporally and spatially controlled by complex intra-molecular autoinhibitory conformation and inter-molecular interactions with protein and lipid partners. The inactivation of FAK in mice results in embryonic lethality attributed to the lack of proper development and function of the heart. Accordingly, embryonic FAK myocyte-specific knockout mice display lethal cardiac defects such as thin ventricle wall and ventricular septum defects. Emerging data also support a role for FAK in the reactive hypertrophy and failure of adult hearts. Moreover, the mechanisms that regulate FAK in differentiated cardiac myocytes to biomechanical stress and soluble factors are beginning to be revealed and are discussed here together with data that connect FAK to its downstream effectors. This article is part of a Special Issue entitled "Local Signaling in Myocytes".
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ABSTRACT: Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols.Tissue Engineering Part B Reviews 02/2012; 18(4):288-300. · 4.64 Impact Factor
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ABSTRACT: Syntenin is an adaptor molecule containing 2 PDZ domains which mediate molecular interactions with diverse integral or cytoplasmic proteins. Most of the results on the biological function of syntenin were obtained from studies with malignant cells, necessitating exploration into the role of syntenin in normal cells. To understand its role in normal cells, we investigated expression and function of syntenin in human lymphoid tissue and cells in situ and in vitro. Syntenin expression was denser in the germinal center than in the extrafollicular area. Inside the germinal center, syntenin expression was obvious in follicular dendritic cells (FDCs). Flow cytometric analysis with isolated cells confirmed a weak expression of syntenin in T and B cells and a strong expression in FDCs. In FDC-like cells, HK cells, most syntenin proteins were found in the cytoplasm compared to weak expression in the nucleus. To study the function of syntenin in FDC, we examined its role in the focal adhesion of HK cells by depleting syntenin by siRNA technology. Knockdown of syntenin markedly impaired focal adhesion kinase phosphorylation in HK cells. These results suggest that syntenin may play an important role in normal physiology as well as in cancer pathology.Immune Network 10/2013; 13(5):199-204.