Phosphatase Subfamily PTPRK

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

PTPRG is a receptor PTP family involved in metazoan neural development and maybe cancer.

Evolution

PTPRK subfamily is vertebrate specific. There are four copies in human.

Domain Structure

PTPRK has dual intracellular catalytic domains. The canonical extracellular domain combination is a MAM domain, Ig domain and multiple FN3 domain.

MAM domain is essential for homophilic cell-cell interaction and helps determine the specificity of these interactions. Truncated PTPRM is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored in a chimeric PTPRM molecule containing the MAM domain of PTPRK. However, this chimeric RPTP mu does not interact with either PTPRK or PTPRM [1].

Functions

PTPRK and PTPRM mediates homophilic cell-cell interaction [1, 2].

PTPRK

PTPRK is a putative tumor suppressor [3] in various types of cancer, such as breast cancer [4], prostate cancer [5] and glioma [6]. It plays its function as tumor suppressor through different mechanisms. For example, i) PTPRK influences transactivating activity of beta-catenin in non-tumoral and neoplastic cells by regulating the balance between signaling and adhesive beta-catenin which is a molecule endowed with a dual function being involved both in cell adhesion and in Wnt signaling pathway [7]. ii) PTPRK is a key factor in coordinating apoptosis via the regulation of MAPK pathways, in particular the JNK pathway in prostate cancer cells [5].

PTPRK dephosphorylates EGFR and thereby regulates Epidermal growth factor receptor (EGFR) tyrosine phosphorylation and subsequent promotes human keratinocyte survival and proliferation [8] (On the other hand, transforming growth factor-beta1 upregulates the expression of PTPRK [9]).

PTPRK regulates CD4+ T cell development through ERK1/2-mediated signaling [10].

References

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