Abstract
Cytokine activity of the isolated recombinant C-terminal domain of mammalian tyrosyl-tRNA synthetase (TyrRS), which is homologous to a tumor-derived cytokine, endothelial and monocyte activating polypeptide (EMAP-2) has been studied. It was shown that C-domain induced a » 2-fold increase of monocyte chemotaxis. This effect is comparable with the values of chemotaxis induction by EMAP-2 cytokine and proEMAP-2. The truncated catalytic form of bovine TyrRS (2 x 39 kDa) has no effect on monocyte chemotaxis. C-domain of TyrRS also induced a « 3-fold increase in tissue factor activity in cultured human endothelial cells. A hypothesis is forwarded that the isolated C-domain of mammalian TyrRS may be released at proteolytic cleavage of TyrRS by some protease, activated at stress conditions, and functions as a mediator via signal transduction through interaction with a putative EMAP-2 receptor.
Highlights
Cytokine activity of the isolated recombinant C-terminai domain of mammalian tyrosyl-tRNA synthetase (TyrRS)1 which is homologous to a tumor-derived cytokine, endothelial and monocyte activating polypeptide (EMAP-2) has been studied
Aminoacyl - t RNA synthetases (ARSases) of higher eukaryotes usually possess amino- and/or carboxy-terminal polypeptide extensions of catalytic enzyme core which are dispensable for their catalytic activities Il—4]
Since EMAP-2 cytokine has been shown to induce migration of monocytes and polymorphonuclear leukocytes in vitro [12, 18], we examined the effects of TyrRS C-domain on monocyte migration, using a micro-chemotaxis chamber assay
Summary
Aminoacyl - t RNA synthetases (ARSases) of higher eukaryotes usually possess amino- and/or carboxy-terminal polypeptide extensions of catalytic enzyme core which are dispensable for their catalytic activities Il—4]. Cytokine activity of the isolated recombinant C-terminai domain of mammalian tyrosyl-tRNA synthetase (TyrRS)1 which is homologous to a tumor-derived cytokine, endothelial and monocyte activating polypeptide (EMAP-2) has been studied. C-domain of TyrRS induced a ~ 3-fold increase in tissue factor activity in cultured human ehdothelial cells.
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