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-k Da tyrosine-threonine dual specificity phosphatase, which has been sho wn 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 lo cated between 80 and 90 nucleotides upstream of the murine PAC-1 initi ation 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 c losely related phophatases, 3CH134 and VH1. The conserved catalytic do main common to all tyrosine phosphatases is encompassed by exon 3. The organization of the murine PAC-1 gene suggests that the PAC-1 N-termi nus, which may serve a regulatory function, has evolved as a separate domain from the C-terminal catalytic domain. (C) 1994 Academic Press, Inc.