Phosphatase Subfamily PTPRD

Phosphatase Classification: Fold CC1: Superfamily CC1: Family PTP: Subfamily PTPRD

PTPRD (LAR) subfamily consists of three members in human.

Evolution

PTPRD subfamily is found in holozoan (metazoan plus it closest relative choanoflagellate). PTPRD subfamily has three gene members in human and most vertebrates: PTPRD, PTPRF and PTPRS. It has single member in most invertebrate metazoan and is under intensive studies in frtui fly. Interestingly, it greatly expanded in sponge.

Domain Structure

All three members of PTPRD subfamily in human has twin intracellular PTP phosphatase domains, and extracellular Ig domains and FN3 domains. Each of them have multiple alternative splicing isoforms (for example, [1]).

Functions

PTPRF (LAR)

The best characterized member of the three human genes in the subfamily is PTPRF, aka LAR. Knock-down of PTPRF by siRNA induced post-receptor insulin resistance with the insulin-induced activation of PKB/Akt and MAP kinases markedly inhibited. But, the phosphorylation and dephosphorylation of the IR and insulin receptor substrate (IRS) proteins were unaffected by PTPRF knock-down [2].

When its 2nd phosphatase was tyrosine phosphorylated by Fyn tyrosine kinase, PTPRF was associated with Fyn Src homology 2 domain and it dephosphorylates phosphorylated tyrosine residues in both the COOH terminus and kinase domain of Fyn in vitro. In addition to Fyn kinase, PTPRF mutants, with Cys to Ser mutation in the catalytic center of 1st phosphatase domain, can bind to tyrosine-phosphorylated Lck kinase [3].

PTPRD

Human PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers [4]. PTPRD loss can cause of aberrant STAT3 activation in gliomas [5]. Human PTPRD is also associated with restless legs syndrome [6], but the underlying mechanism is unclear. PTPRD interacts with MIM-B, a putative metastasis suppressor protein binding to actin [7]. It is not clear whether MIM-B is its substrate. The 2nd phosphatase domain of PTPRD can bind to inhibit the 1st phosphatase domain of PTPRS [8].

References

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