3 DISTINCT HUMAN THYMOPOIETINS ARE DERIVED FROM ALTERNATIVELY SPLICEDMESSENGER-RNAS

Thymopoietin (TP) was originally isolated as a 5-kDa 49-aa protein fro m bovine thymus in studies of the effects of thymic extracts on neurom uscular transmission and was subsequently observed to affect T-cell di fferentiation and function. We now report the isolation of cDNA clones for three alternatively spliced mRNAs that encode three distinct huma n T-cell TPs. Proteins encoded by these mRNAs, which we have named TP alpha (75 kDa), TP beta (51 kDa), and TP gamma (39 kDa), contain ident ical N-terminal regions, including sequences nearly identical to that of the originally isolated 49-aa protein, but divergent C-terminal reg ions. TP mRNAs are expressed in many tissues, most abundantly in adult thymus and fetal liver of the tissues so far examined. Distinct struc tural domains and functional motifs in TPs alpha, beta, and gamma sugg est that the proteins have unique functions and may be directed to dis tinct subcellular compartments.