Protein Tyrosine Phosphatases in the Human Genome

Abstract

Tyrosine phosphorylation is catalyzed by protein tyrosine kinases, which are represented by 90 genes in the human genome. Here, we present the set of 107 genes in the human genome that encode members of the four protein tyrosine phosphatase (PTP) families. The four families of PTPases, their substrates, structure, function, regulation, and the role of these enzymes in human disease will be discussed.

Paladin (X99384) is expressed in the vasculature and shifts from endothelial to vascular smooth muscle cells during mouse development

“…Even though Paladin has four predicted S/T/Y phosphatase domains and negatively regulates insulin receptor tyrosine kinase and AKT phosphorylation Huang and coworkers could not confirm phosphatase activity of the protein (Huang et al, 2009). The members of the PTP superfamily can be divided into four main subfamilies, type 1 through 4, based on their amino acid sequence and presence of functional domains, reviewed in (Alonso et al, 2004) and (Mustelin, 2007). The human fulllength Paladin gene displays a weak homology to DUSP23 (dual specificity phosphatase 23), which belongs to PTP subfamily 1.…”

PTPN22 and rheumatoid arthritis: Gratifying replication

“…As noted above, PTPN22 belongs to a family of intracellular tyrosine phosphatases (14). It has been known for more than a decade that tyrosine phosphatase activity is associated with a negative regulatory effect on T cell function.…”

“…Indeed, there is now an explosion of interest in phosphatases as regulators of a wide variety of cellular functions (21). More than 100 different tyrosine phosphatases have been defined; this exceeds the number of tyrosine kinases (14). Although all of these molecules are likely to have interesting biologic effects (21), PTPN22 is now going to receive a high level of scrutiny, given its clear involvement in RA and other forms of autoimmunity.…”

Epigenetic regulation of protein tyrosine phosphatases: potential molecular targets for cancer therapy

“…Alteration in the expression or function of these PTPs could, therefore, lead to deregulation of tightly regulated signaling process resulting in uncontrolled cell growth among other pathological conditions. 26 In addition to the functional consequences that would arise upon loss of a PTP, genetic alterations of several PTPs in different types of cancers also strengthen their position as growth/tumor suppressors (see Table 1). Several PTPs (e.g.…”

“…30 A recent study based on computational analysis of the human genome identified 38 classical PTPs, 19 of which mapped to regions frequently deleted in human cancers and 30 of these protein phosphatases have been implicated in different types of cancers. 26,31 Several studies have implicated PTPs in cancer and a few have demonstrated their role as tumor suppressors using in vitro and in vivo assays. 32 To this date, however, DEP1 is the only protein tyrosine phosphatase that is classified as an authentic tumor suppressor.…”