RK-682, A POTENT INHIBITOR OF TYROSINE PHOSPHATASE, ARRESTED THE MAMMALIAN-CELL CYCLE PROGRESSION AT G(1)PHASE

A specific inhibitor of protein tyrosine phosphatase (PTPase), RK-682 (3-hexadecanoyl-5-hydrosymethyl-tetronic acid) was isolated from microbial metabolites, In vitro, RK-682 inhibited dephosphorylation activity of CD45 and VHR with IC50 54 and 2.0 mu M, respectively, In situ, sodium orthovanadate and RK-682 enhanced the phosphotyrosine level of Ball-1 cells, a human B cell leukemia, but not the phosphoserine/threonine level. The PTPase inhibitors, however, had the different arrest point on the cell cycle progression, Sodium orthovanadate inhibited the cell cycle progression at G(2)/M boundary phase, on the other hand, RK-682 inhibited the G(1)/S transition.