Structure of the gene encoding the murine dual specificity tyrosine- threonine phosphatase PAC1

The mitogen-induced early-response gene, PAC-1, encodes a nuclear 32-kDa tyrosine-threonine dual specificity phosphatase, which has been shown to specifically dephosphorylate the mitogen activated protein (MAP) kinases, ERK1 and ERK2. Here, we describe the structure and sequence of the murine PAC-1 gene. Transcription starts at three major sites located between 80 and 90 nucleotides upstream of the murine PAC-1 initiation codon within a highly G/C-rich region. The gene comprises three exons, with exon 1 encoding the unique N-terminal half of the protein, while exons 2 and 3 encode the C- terminus that is homologous to the closely related phophatases, 3CH134 and VH1. The conserved catalytic domain common to all tyrosine phosphatases is encompassed by exon 3. The organization of the murine PAC-1 gene suggests that the PAC-1 N-terminus, which may serve a regulatory function, has evolved as a separate domain from the C-terminal catalytic domain.