Abstract
Human p43 is associated with macromolecular tRNA synthase complex and known as a precursor of endothelial monocyte-activating polypeptide II (EMAP II). Interestingly, p43 is also secreted to induce proinflammatory genes. Although p43 itself seems to be a cytokine working at physiological conditions, most of the functional studies have been obtained with its C-terminal equivalent, EMAP II. To gain an insight into the working mechanism of p43/EMAP II, we used EMAP II and searched for an interacting cell surface molecule. The level of EMAP II-binding molecule(s) was significantly increased in serum-starved tumor cells. Thus, the EMAP II-binding molecule was isolated from the membrane of the serum-starved CEM cell. The isolated protein was determined to be the alpha subunit of ATP synthase. The interaction of EMAP II and alpha-ATP synthase was confirmed by enzyme-linked immunosorbent assay and in vitro pull down assays and blocked with the antibodies raised against EMAP II and alpha-ATP synthase. The binding of EMAP II to the surface of serum-starved cells was inhibited in the presence of soluble alpha-ATP synthase. EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble alpha-ATP synthase. Anti-alpha-ATP synthase antibody also showed an inhibitory effect on the proliferation of endothelial cells mimicking the activity of EMAP II. These results suggest the potential interaction of p43/EMAP II with alpha-ATP synthase and its role in the proliferation of endothelial cells.
Highlights
Human p43 is associated with macromolecular tRNA synthase complex and known as a precursor of endothelial monocyte-activating polypeptide II (EMAP II)
The staining with EMAP II was mainly detected on the surface of CEM cells cultured in the serum-free medium, confirming that the binding of EMAP II was increased on the cell surface by serum starvation (Fig. 1B)
To gain an insight into the function of EMAP II through ␣-ATP synthase, we investigated whether ␣-ATP synthase is involved in the inhibition of the endothelial cells (ECs) proliferation by EMAP II
Summary
Human p43 is associated with macromolecular tRNA synthase complex and known as a precursor of endothelial monocyte-activating polypeptide II (EMAP II). The binding of EMAP II to the surface of serum-starved cells was inhibited in the presence of soluble ␣-ATP synthase. EMAP II inhibited the growth of endothelial cells, and this effect was relieved by soluble ␣-ATP synthase. Anti␣-ATP synthase antibody showed an inhibitory effect on the proliferation of endothelial cells mimicking the activity of EMAP II. In addition to the induction of tissue factor-dependent coagulation on ECs and monocytes, EMAP II up-regulates endothelial E-selectin and P-selectin expression and induces the release of von Willebrand factor. Proliferation assays suggested that both EMAP II and anti-␣-ATP synthase antibodies inhibit EC proliferation, and the inhibitory effect of EMAP II on the EC proliferation was abrogated in the presence of soluble ␣-ATP synthase. These results imply that EMAP II binding to the ␣-ATP synthase may be involved in the inhibition of the EC proliferation
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