title: Transglutaminase-2 in cell adhesion: all roads lead to paxillin?
abstract: Cell-matrix adhesion is a fundamental biological process that governs survival, migration, and proliferation of living eukaryotic cells. Paxillin is an important central player in a network of adhesome proteins that form focal adhesion complexes. Phosphorylation of tyrosine and serine residues in paxillin is critical for the coordinated sequential recruitment of other adaptor and kinase proteins to adhesion complexes. Recently, the phosphorylation of serine178 in paxillin has been shown to be vital for epithelial cell adhesion and migration. In vivo and in vitro evidence have shown that transglutaminase (TG)-2 positively regulates this phosphorylation. Here, we propose three possible mechanisms that may explain these observations. First, TG-2 itself may be an adhesome member directly interacting with paxillin in a non-covalent way. Second, TG-2 may cross link a mitogen-activated protein kinase kinase kinase (MAP3K), which eventually activates c-Jun N-terminal kinase (JNK), and the latter phosphorylates paxillin. Lastly, TG-2 may have intrinsic kinase activity that phosphorylates paxillin. Future studies investigating these hypotheses on TG-2-paxillin relationships are necessary in order to address this fundamental process in cell matrix adhesion signaling.
authors.affiliation: Ocular Surface Research Group; Singapore Eye Research Institute; Singapore.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Png
authors.affiliation: Ocular Surface Research Group; Singapore Eye Research Institute; Singapore; Department of Cornea and External Eye Disease; Singapore National Eye Center; Singapore; Office of Clinical Science; Duke-NUS Graduate Medical School; Singapore; Department of Ophthalmology; Yong Loo Lin School of Medicine; National University of Singapore; Singapore.
authors.forename: Louis
authors.initials: L
authors.lastname: Tong
mesh_terms: D002448:Cell Adhesion / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015398:Signal Transduction; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
chemical_list: D051419:Paxillin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D048031:JNK Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins
keywords: adhesion; adhesome; cell culture; migration; paxillin; review; signaling; transglutaminase