Tryptophanyl-tRNA synthetase (TrpRS) expression alters in colorectal (CRC), pancreatic (PC), and cervical (CC)
cancers. Here, phosphorylation of unfolded TrpRS and its fragments is stimulated by human
cancer sera (CS; n = 13) and serum of rabbit
tumor induced by Rous sarcoma virus, unaffected by donor sera (
NS; 11/15) and abolished by
alkaline phosphatase. At 20 years of follow-up, serum-inducible TrpRS phosphorylation found years before healthy donors (3/15) diagnosed with PC, CRC, or
leukemia. I have examined a specificity of serum-inducible TrpRS phosphorylation and found, surprisingly, that
serine phosphorylation of unfolded TrpRS is stimulated by anti-TrpRS rabbit
antisera but is unaffected by rabbit nonimmune sera and
antisera to other
antigens. Anti-TrpRS
immunoglobulin G (
IgG) inhibits phosphorylation of full-length TrpRS and stimulates phosphorylation of its 20-kDa fragment. Phosphorylation of this fragment is stimulated also by CS but not NS.
2-Mercaptoethanol and
cyclic AMP exerted synergistic inhibitory effect on TrpRS phosphorylation. Anti-TrpRS sera and
casein act as chaperones increasing TrpRS phosphorylation through refolding.
Histone-specific
protein kinase activity in CS (n = 44) and anti-TrpRS sera was lower than that in NS (n = 11), rabbit nonimmune sera and
antisera to other
antigens. TrpRS inhibitors,
tryptamine, and
tryptophanol stimulate in vivo accumulation of enzymatically inactive, nonphosphorylated, aggregated and anti-TrpRS
IgG refoldable TrpRS. Phosphorylation of postsurgical tissues (n = 18) reveals TrpRS in
ovarian cancer (OVC) and CC but not in normal placenta and liver. In OVC, TrpRS phosphorylation increase correlates with elevated
tryptophan-dependent
ATP-inorganic
pyrophosphate exchange. Although not inducing
cancer, TrpRS triggers signaling concomitant with
cancer.