Prenylation of oncogenic human PTPCAAX protein tyrosine phosphatases

Many isoprenylated proteins are known to participate in signal transduction, but not all have been identified. Using an in vitro prenylation screen, two human cDNAs (PTPCAAXI and PTPCAAX2) homologous to the rat PRL-1 and human OV-1 protein tyrosine phosphatase genes were identified. PTPCAAXI and PTPCAAX2 were farnesylated in vitro by mammalian farnesyl:protein transferase, and epitope-tagged PTPCAAX2 was prenylated in epithelial cells. Overexpression of PTPCAAXI and PTPCAAX2 in epithelial cells caused a transformed phenotype in culture and tumor growth in nude mice. Thus, PTPCAAXI and PTPCAAX2 represent a novel class of isoprenylated, oncogenic protein tyrosine phosphatases.