ENHANCED EXPRESSION OF MULTIPLE PROTEIN-TYROSINE PHOSPHATASES IN THE REGENERATING MOUSE-LIVER - ISOLATION OF PTP-RL10, A NOVEL CYTOPLASMIC-TYPE PHOSPHATASE WITH SEQUENCE HOMOLOGY TO CYTOSKELETAL PROTEIN-4.1

To elucidate the role that protein tyrosine phosphatases (PTPs) may pl ay in liver regeneration, PTPs expressed in the mouse liver after part ial hepatectomy (PH) were investigated by a PCR-based cloning method, Sequencing of 115 cDNA clones identified 10 different sequences includ ing MPTP (T cell PTP), PTP-1B, PTP-P19, mR-PTP mu, R-PTP alpha, PTP NE -3 (PTP-P1), R-PTP-kappa and the murine homologue of human LAR, The re maining two sequences, PTP-RL9 and PTP-RL10, encoded novel PTPs. PTP-R L10 cDNA contained an open reading frame of 1176 amino acids with no a pparent membrane-spanning region. The amino-terminal region had sequen ce homology to those of human erythrocyte protein 4.1 and ezrin, cytos keletal proteins. In the regenerating liver, the levels of five PTP ge ne mRNAs (MPTP, PTP-P19, R-PTP alpha, LAR homologue, and PTP-RL9) incr eased within 6h, decreased to the normal level by 24h, and increased a gain at 48 to 72 h after PH, The levels of PTP-1B and R-PTP-kappa mRNA s peaked within 6 h, decreased gradually, and returned to the normal l evel by 168 h after PH, In contrast, the levels of two PTP mRNAs (mR-P TP mu and PTP-RL10) peaked at 48 to 72 h, and returned to the normal l evel by 168 h after PH, No expression of PTP NE-3 was detected in the liver by Northern blotting, The differential expression of multiple PT Ps during the prereplicative and post-replicative stages of liver rege neration suggests that PTPs are involved in the regulation of growth a nd differentiation of liver cells.