PRL-1, a unique nuclear protein tyrosine phosphatase, affects cell growth.
PRL-1 is a particularly interesting immediate-early gene because it is induced in mitogen-stimulated cells and regenerating liver but is constitutively expressed in insulin-treated rat H35 hepatoma cells, which otherwise show normal regulation of immediate-early genes. PRL-1 is expressed throughout the course of hepatic regeneration, and its expression is elevated in a number of tumor cell lines. Sequence analysis reveals that PRL-1 encodes a 20-kDa protein with an eight-amino-acid consensus protein tyrosine phosphatase (PTPase) active site. PRL-1 is able to dephosphorylate phosphotyrosine substrates, and mutation of the active-site cysteine residue abolishes this activity. As PRL-1 has no homology to other PTPases outside the active site, it is a new type of PTPase. PRL-1 is located primarily in the cell nucleus. Stably transfected cells which overexpress PRL-1 demonstrate altered cellular growth and morphology and a transformed phenotype. It appears that PRL-1 is important in normal cellular growth control and could contribute to the tumorigenicity of some cancer cells.
Diamond
R H
RH
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145.
Cressman
D E
DE
Laz
T M
TM
Abrams
C S
CS
Taub
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D016384:Consensus Sequence; D017931:DNA Primers; D017781:Genes, Immediate-Early; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D017931:DNA Primers; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C490198:PTP4A1 protein, human; D017027:Protein Tyrosine Phosphatases; C490199:Ptp4a1 protein, rat