Protein Tyrosine Phosphatases: A Diverse Family of Intracellular and Transmembrane Enzymes

Abstract

Protein tyrosine phosphatases (PTPs) represent a diverse family of enzymes that exist as integral membrane and nonreceptor forms. The PTPs, with specific activities in vitro 10 to 1000 times greater than those of the protein tyrosine kinases would be expected to effectively control the amount of phosphotyrosine in the cell. They dephosphorylate tyrosyl residues in vivo and take part in signal transduction and cell cycle regulation. Most of the transmembrane forms, such as the leukocyte common antigen (CD45), contain two conserved intracellular catalytic domains; but their external segments are highly variable. The structural features of the transmembrane forms suggest that these receptor-linked PTPs are capable of transducing external signals; however, the ligands remain unidentified. A hypothesis is proposed explaining how phosphatases might act synergistically with the kinases to elicit a full physiological response, without regard to the state of phosphorylation of the target proteins.