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Amino Acids. 2017 Mar;49(3):473-481. doi: 10.1007/s00726-016-2331-z. Epub 2016 Sep 16.

Transglutaminase type 2 affects cell migration through post-translational modification of platelet-derived growth factor-BB.

Author information

1
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
2
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. claudiotabolacci@tiscali.it.
3
CNR, Istituto di Scienze dell'Alimentazione, Avellino, Italy.
4
Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Fondazione Luigi Maria Monti, Rome, Italy.
5
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. francesco.facchiano@iss.it.

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.

KEYWORDS:

Angiogenesis; Cancer; Migration; PDGF; Serum; Transglutaminase type 2

PMID:
27633721
DOI:
10.1007/s00726-016-2331-z
[Indexed for MEDLINE]

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