Signal transduction via
tyrosine phosphorylation, normally fine-tuned by the concerted action of both
protein tyrosine kinases and
protein tyrosine phosphatases (
PTPs), is a key mechanism in
tumorigenesis.
PTP-PEST, a ubiquitously expressed cytoplasmic
tyrosine phosphatase, is thought to play an important role in cell adhesion and motility, and may be involved in
metastasis. A search for sequence variations within the gene PTPN12 (alias
PTP-PEST) was performed in
breast cancer cell lines, leading to the identification of three amino acid substitutions at positions 322, 573, and 709. These alterations were also found in
squamous cell carcinoma cell lines and could be verified in primary human breast and kidney
tumor samples. Analysis of peripheral blood samples confirmed the germline origin of these alterations. Furthermore, functional characterization of the Ile322 and Ala573
PTP-PEST mutants revealed an enhancement of in vitro
phosphatase activity, whereas the Lys709 variant showed reduced catalytic activity. These data demonstrate the existence of
PTP-PEST variants that might be meaningful for human
cancer and underscore the need for further characterizing
PTP-PEST and its signaling pathways in context of this disease.