The human prothymosin alpha gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA.

Abstract

Clones from human prothymosin .alpha. have been identified in cDNA libraries from staphylococcal enterotoxin A-stimulated normal human lymphocytes and from simian virus 40-transformed fibroblasts. The 1198-base-pair fibroblast clone has been sequenced. The encoded protein is highly acidic (54 residues out of 111) and shares > 90% sequence homology with rat prothymosin .alpha.. The peptide "hormone" thymosin .alpha.1 appears at positions 2-29 of the prothymosin .alpha. amino acid sequence. There is no N-terminal signal peptide. Examination of mouse and human tissues revealed the presence of prothymosin .alpha. mRNA in kidneys, liver, spleen, normal lymphocytes (predominantly T cells), human T-cell leukemia virus-infected T cells, and myeloma cells (B-cell lineage). Prothymosin .alpha. mRNA is inducible; upon mitogen stimulation it increased > 15-fold above the level found in resting lymphocytes. Similarly, serum-derived NIH 3T3 cells responded to serum restitution with an increase in prothymosin .alpha. mRNA. Characterization of human genomic DNA by Southern blot analysis disclosed a complicated pattern consistent with genetic polymorphism. These data suggest that prothymosin .alpha. plays an intracellular role tied to cell proliferation. There is no evidence that it serves as a precursor for secreted thymic peptides. However, given the complexity at the genomic level, multiple functions, including a putative secretory capability, cannot be excluded.