17 - Protein dephosphorylation and protein phosphorylation

Abstract

The phosphorylation of proteins, at serine, threonine or tyrosine residues, serves multiple roles in the regulation of cell function. However, dephosphorylation is as important as phosphorylation, and it follows that the phosphoprotein phosphatases are integral components of the signaling systems operated by protein kinases. In a number of cases dephosphorylation serves as a true reset button, bringing proteins back to their resting state. The chapter describes the roles of protein tyrosine phosphatases (PTPs) and serine–threonine-specific phosphatases in phosphorylation and dephosphorylation. PTPs are a family of multi-domain proteins, which can be broadly divided into two groups, the transmembrane or receptor-like PTPs and the cytosolic PTPs. Examples of positive regulation of signal transduction through phosphotyrosine dephosphorylation include the phosphatase activity of CD45, and positive signal downstream of receptor tyrosine kinase activation by SHP-2 (Src homology phosphatase-2). Examples of negative regulation of signal transduction through dephosphorylation include MAP kinase phosphatase-1(MKP-1), which attenuates the growth factor signal of MAP kinase; SHP-1, which has down-regulatory effect on a number of signal transduction pathways; and PTEN (phosphatase and tensin homologue deleted from chromosome-10), which dephosphorylates phosphatidylinositol (3,4,5)-triphosphate (PIP3). Unlike PTPs, which are all monomeric, the serine–threonine phosphatases are oligomeric and characterized by their association with targeting subunits. The chapter describes the classification of serine–threonine phosphatases and discusses the role of Ser/Thr phosphatase Protein phosphatase I (PPI) in the regulation of glycogen metabolism and the role of PP2B (calcineurin) in regulation of T-cell proliferation.