Oligonucleotide probes corresponding to three invariant amino acid sequence motifs within the protein tyrosine phosphatase (PTPase) catalytic domain were synthesized and employed in the polymerase chain reaction (PCR). PCR products amplified from human colonic tissues were analyzed. Among 41 cDNA clones sequenced, two putative novel PTPases designated as CL-6 and CL-2B were isolated. cDNA cloning of CL-6 was performed, and three overlapped cDNA clones encoding part of the coding region, which was 2.1 kb long, were obtained. Expression of mRNAs of these clones was then investigated by Northern blot analysis or reverse transcriptase-PCR, suggesting that CL-6 mRNA may be expressed in a cell-type-specific manner, whereas the expression of CL-2B mRNA could be ubiquitous.