Phosphatase Subfamily PTPN6

Phosphatase Classification: Fold CC1:Superfamily CC1: Family PTP: Subfamily PTPN6 (SHP)

Evolution

The PTPN6 subfamily is found across holozoa. It is a single copy in most invertebrate genomes and two or three copies in most vertebrates. Human has two members, PTPN6 (SHP1) and PTPN11 (SHP2).

Domain

The PTPN6 subfamily has two tandem SH2 domains and phosphatase domain. Besides the structural domains, it has a C-terminal tail important for the regulation of its function [1].

Functions

Human PTPN6 (SHP-1) and PTPN11 (SHP-2) are proposed to have different roles in signal transduction: PTPN6/SHP-1 plays a largely negative signalling role, whereas PTPN11/SHP-2 plays a largely positive role in cell signalling leading to cell activation. Expression of PTPN6/SHP-1 is restricted mainly to haematopoietic cells whereas PTPN11/SHP-2 is more widely expressed; both enzymes are expressed in many haematopoietic cells [1].

The PTPN6/SHP subfamiy is under extensive studies and see more in reviews (e.g. [2, 3]) and papers.

Temporary

PTPN6/SHP-1 dephosphorylates and inhibites Transient receptor potential vanilloid 1 (TRPV1) receptors in rat dorsal root ganglions (DRGs) [4]. TRPV1 is a nonselective cation channel that provides sensation of scalding heat and pain (nociception).

PKA phosphorylates PTPN11/SHP-2 at Thr-73 and Ser-189 in two SH2 domains, respectively. The phosphorylation inhibits ligand-binding mediated by SH2 domains and phosphatase activity [5].

References

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