Cloning and characterization of PTPL1, a protein tyrosine phosphatase with similarities to cytoskeletal-associated proteins.

Abstract

A novel cytoplasmic protein tyrosine phosphatase (PTP), PTPL1, was identified and cloned using a polymerase chain reaction-based approach. Overlapping cDNA clones encompass an open reading frame of 7398 base pairs, predicting a protein of 2466 amino acid residues with a molecular mass of 275 kDa. PTPL1 has a wide tissue distribution, a 9.5-kilobase transcript being expressed in most tissues. Peptide antisera against PTPL1 specifically precipitate a protein with an apparent mass of 250 kDa. PTPL1 has a PTP domain located in the COOH terminus, and the protein was shown to dephosphorylate 32P-labeled myelin basic protein. In the non-enzymatic part of PTPL1, three different structural motifs can be identified. Two of these are often found in proteins at the interface between the plasma membrane and the cytoskeleton, i.e. a 300-amino acid domain with similarity to the band 4.1 superfamily, and a region consisting of five GLGF repeats, an 80-amino acid repeat found in a variety of cytoskeleton-associated proteins. In addition to these structures PTPL1 has a region that fulfills the criteria for a leucine zipper motif. PTPL1 is the hitherto largest PTP identified and the only one known which contains a leucine zipper motif.