title: Transglutaminase type 2 affects cell migration through post-translational modification of platelet-derived growth factor-BB.
abstract: Migration is a key cellular function with important implications in cell physiology. Impairment of such function is observed in angiogenesis, cancer, central nervous system development, and many other physiological and pathological events. Serum is considered among the most potent physiological chemotactic stimuli. Transglutaminase 2 (TG2) is involved in most of the mentioned processes, suggesting the hypothesis that TG2 may modulate cell movement and chemotaxis by acting on serum factors. Cell biology and biochemistry studies confirmed this hypothesis, showing that human serum contains potent chemotactic signals significantly impaired by activated TG2. Bioinformatics studies indicated that one potent serum factor potential substrate of TG2-dependent transamidation is platelet-derived growth factor-BB (PDGF-BB). Cell biology and immunometric experiments carried out with U87MG human glioma cell line showed that human recombinant PDGF-BB pre-incubated with calcium-activated TG2 lost about 70 % of its chemotactic activity and antigenicity. These data indicate that PDGF-BB is a substrate of TG2-transamidating activity, and such modification may play a key role in the modulation of PDGF's chemotactic features. Further, these findings suggest a novel point of view to study the extracellular functions of TG2 and to understand how protein signals, such as growth factors and cytokines, act in the extracellular space to reach their specific targets.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Cordella
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. claudiotabolacci@tiscali.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tabolacci
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Senatore
authors.affiliation: CNR, Istituto di Scienze dell'Alimentazione, Avellino, Italy.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Facchiano
authors.affiliation: Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Fondazione Luigi Maria Monti, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Arcangelo
authors.affiliation: Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Fondazione Luigi Maria Monti, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Facchiano
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. francesco.facchiano@iss.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Facchiano
mesh_terms: D000077214:Becaplermin; D002118:Calcium / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000819:agonists / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011499:Protein Processing, Post-Translational; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002118:Calcium
keywords: Angiogenesis; Cancer; Migration; PDGF; Serum; Transglutaminase type 2