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 phosphatase (PTPs) may play in liver regeneration, PTPs expressed in the mouse liver after partial hepatectomy (PH) were investigated by a PCR-based cloning method. Sequencing of 115 cDNA clones identified 10 different sequences including 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 remaining two sequences, PTP-RL9 and PTP-RL10, encoded novel PTPs. PTP-RL10 cDNA contained an open reading frame of 1176 amino acids with no apparent membrane-spanning region. The amino-terminal region had sequence homology to those of human erythrocyte protein 4.1 and ezrin, cytoskeletal proteins. In the regenerating liver, the levels of five PTP gene mRNAs (MPTP, PTP-P19, R-PTP alpha, LAR homologue, and PTP-RL9) increased within 6 h, decreased to the normal level by 24 h, and increased again at 48 to 72 h after PH. The levels of PTP-1B and R-PTP-kappa mRNAs peaked within 6 h, decreased gradually, and returned to the normal level by 168 h after PH. In contrast, the levels of two PTP mRNAs (mR-PTP mu and PTP-RL10) peaked at 48 to 72 h, and returned to the normal level by 168 h after PH. No expression of PTP NE-3 was detected in the liver by Northern blotting. The differential expression of multiple PTPs during the pre-replicative and post-replicative stages of liver regeneration suggests that PTPs are involved in the regulation of growth and differentiation of liver cells.