Protein tyrosine phosphatases (PTPases) are a family of enzymes important in cellular regulation. Characterization of two cDNAs encoding intracellular PTPases expressed primarily in hematopoietic tissues and cell lines has revealed proteins that are potential regulators of signal transduction. One of these, SHP (Src homology region 2 [SH2]-domain phosphatase), possesses two tandem SH2 domains at the amino terminus of the molecule. SH2 domains have previously been described in proteins implicated in signal transduction, and SHP may be one of a family of nonreceptor PTPases that can act as direct antagonists to the nonreceptor protein tyrosine kinases. The SH2 domains of SHP preferentially bind a 15,000-Mr protein expressed by LSTRA cells. LSTRA cells were shown to express SHP protein by immunoprecipitation, thus demonstrating a potential physiological interaction. The other PTPase, PEP (proline-, glutamic acid-, serine-, and threonine-rich [PEST]-domain phosphatase), is distinguished by virtue of a large carboxy-terminal domain of approximately 500 amino acids that is rich in PEST residues. PEST sequences are found in proteins that are rapidly degraded. Both proteins have been expressed by in vitro transcription and translation and in bacterial expression systems, and both have been demonstrated to have PTPase activity. These two additional members of the PTPase family accentuate the variety of PTPase structures and indicate the potential diversity of function for intracellular tyrosine phosphatases.
Characterization of two structurally related Xenopus laevis protein tyrosine phosphatases with homology to lipid-binding proteins.
