title: Nuclear FAK: a new mode of gene regulation from cellular adhesions.
abstract: Focal adhesion kinase (FAK) is a protein tyrosine kinase (PTK) crucial in regulation of cell migration and proliferation. In addition to its canonical roles as a cytoplasmic kinase downstream of integrin and growth factor receptor signaling, recent studies revealed new aspects of FAK action in the nucleus. Nuclear FAK promotes p53 and GATA4 degradation via ubiquitination, resulting in enhanced cell proliferation and reduced inflammatory responses. FAK can also serve as a co-transcriptional regulator that alters a gene transcriptional activity. These findings established a new paradigm of FAK signaling from cellular adhesions to the nucleus. Although physiological stimuli for controlling FAK nuclear localization have not been completely characterized, FAK shuttles from focal adhesions to the nucleus to directly convey extracellular signals. Interestingly, nuclear translocation of FAK becomes prominent in kinase-inhibited conditions such as in de-adhesion and pharmacological FAK inhibition, while a small fraction of nuclear FAK is observed a normal growth condition. In this review, roles of nuclear FAK in regulating transcription factors will be discussed. Furthermore, a potential use of a pharmacological FAK inhibitor to target nuclear FAK function in diseases such as inflammation will be emphasized.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, USA. stlim@southalabama.edu
authors.forename: Ssang-Taek Steve
authors.initials: ST
authors.lastname: Lim
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002467:Cell Nucleus / Q000201:enzymology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D022001:Focal Adhesions / Q000201:enzymology; D005786:Gene Expression Regulation; D006801:Humans; D015398:Signal Transduction / Q000235:genetics
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases