5f28
From Proteopedia
Crystal structure of FAT domain of Focal Adhesion Kinase (FAK) bound to the transcription factor MEF2C
Structural highlights
FunctionMEF2C_MOUSE Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. May also be involved in neurogenesis and in the development of cortical architecture. Isoform 3 and isoform 4, which lack the repressor domain, are more active than isoform 1, isoform 2 and isoform 5 (By similarity). Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells.[UniProtKB:Q06413][1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedFocal adhesion kinase (FAK) has emerged as a mediator of mechanotransduction in cardiomyocytes, regulating gene expression during hypertrophic remodeling. However, how FAK signaling is relayed onward to the nucleus is unclear. Here, we show that FAK interacts with and regulates myocyte enhancer factor 2 (MEF2), a master cardiac transcriptional regulator. In cardiomyocytes exposed to biomechanical stimulation, FAK accumulates in the nucleus, binds to and upregulates the transcriptional activity of MEF2 through an interaction with the FAK focal adhesion targeting (FAT) domain. In the crystal structure (2.9 A resolution), FAT binds to a stably folded groove in the MEF2 dimer, known to interact with regulatory cofactors. FAK cooperates with MEF2 to enhance the expression of Jun in cardiomyocytes, an important component of hypertrophic response to mechanical stress. These findings underscore a connection between the mechanotransduction involving FAK and transcriptional regulation by MEF2, with potential relevance to the pathogenesis of cardiac disease. FAK Forms a Complex with MEF2 to Couple Biomechanical Signaling to Transcription in Cardiomyocytes.,Cardoso AC, Pereira AHM, Ambrosio ALB, Consonni SR, Rocha de Oliveira R, Bajgelman MC, Dias SMG, Franchini KG Structure. 2016 Aug 2;24(8):1301-1310. doi: 10.1016/j.str.2016.06.003. Epub 2016 , Jul 14. PMID:27427476[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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