PTPN13

Fig1. Scheme of PTPL1domains and interacting partners. Arrow from the catalytic domain points direct substrates (black) and putative substrates (grey). (Gilles Freiss, 2011)

What is PTPN13 protein?

PTPN13 (protein tyrosine phosphatase non-receptor type 13) gene is a protein coding gene which situated on the long arm of chromosome 4 at locus 4q21. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. PTPN13 also known as PTPL1, is a large protein that possesses a PTP domain at C-terminus, and multiple noncatalytic domains, which include a domain with similarity to band 4.1 superfamily of cytoskeletal-associated proteins, a region consisting of five PDZ domains, and a leucine zipper motif. The PTPN13 protein is consisted of 2485 amino acids and its molecular mass is approximately 276.9 kDa.

What is the function of PTPN13 protein?

PTPN13 is a protein tyrosine phosphatase that regulates intracellular signaling by dephosphorylation of specific signaling molecules. PTPN13 plays a role in multiple biological processes, including cell proliferation, differentiation, migration, and apoptosis. It is particularly important in the immune response, regulating the activation of T and B cells as well as the inflammatory response. In addition, PTPN13 is involved in bone development and metabolism, as well as signaling pathways associated with tumorigenesis and development.

PTPN13 Related Signaling Pathway

PTPN13 is involved in several signaling pathways, including EGFR, NF-κB, Wnt/β-catenin, etc. In these signaling pathways, PTPN13 regulates the activity of several key regulatory factors through dephosphorylation, thereby affecting biological processes such as cell proliferation, differentiation, survival, and migration.

PTPN13 Related Diseases

In terms of immune diseases, abnormal activity of PTPN13 is associated with the occurrence of autoimmune diseases, for example, defects or dysfunction of PTPN13 may lead to inadequate or excessive immune response, which can trigger diseases such as rheumatoid arthritis and systemic lupus erythematosus. In the skeletal system, PTPN13 is involved in regulating the function of bone cells and bone metabolism, and its dysfunction may be associated with the development of diseases such as osteoporosis. In addition, the role of PTPN13 in tumorigenesis and development has also attracted the attention of researchers, including a variety of malignant tumors such as breast cancer, colorectal cancer, stomach cancer and lung cancer.

Bioapplications of PTPN13

Due to its important role in the immune and skeletal systems, PTPN13 is seen as a potential therapeutic target for diseases such as autoimmune disorders and osteoporosis. Small molecule inhibitors or activators targeting PTPN13 are being investigated to evaluate their potential value for disease treatment.

Case study 1: Jing Wang, 2022

To reveal the function of protein tyrosine phosphatase-L1 (PTPL1) in lung adenocarcinoma. Lung cancer cell lines were transfected with short hairpin RNA against PTPL1 (shPTPL1 group) or negative control (shmock group). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to verify the transfection efficacy. Cell proliferation was analyzed and colony formation assay after PTPL1 or PTPL1 and yes-associated protein (YAP1) knockdown.

PTPL1 was downregulated in various types of lung cancer cell lines. PTPL1 knockdown increased the proliferation of lung cancer cells. Mechanistically, PTPL1 knockdown induced the activation of the Proto-oncogene tyrosine-protein kinase SRC (Src)/Extracellular regulated MAP kinase (ERK) pathway and thereby promoted yes-associated protein (YAP1) nuclear translocation and activation.

Fig1. Knockdown of PTPL1 was validated via western blot analyses. PTPL1, protein-tyrosine phosphatase-L1; shmock, negative control; shPTPL1, short hairpin RNA against PTPL1.

Fig2. PTPL1 knockdown facilitates NSCLC cell proliferation in vitro. Cell proliferation was analyzed by immunofluorescence staining for EdU.

Case study 2: Mohamed Hamyeh, 2020

Clinical data suggest that the protein tyrosine phosphatase PTPN13 exerts an anti-oncogenic effect. Its exact role in tumorigenesis remains, however, unclear due to its negative impact on FAS receptor-induced apoptosis.

The team crossed transgenic mice deleted for PTPN13 phosphatase activity with mice that overexpress human HER2 to assess the exact role of PTPN13 in tumor development and aggressiveness. They also developed isogenic clones of the aggressive human breast cancer cell line MDA-MB-231 overexpressing either wild type or a catalytically-inactive mutant PTPN13. The results showed that observed that PTPN13 phosphatase activity is required to inhibit cell motility and invasion in the MDA-MB-231 cell line overexpressing PTPN13. Phosphoproteomic and gene ontology analyses indicated a role of PTPN13 in the regulation of intercellular junction-related proteins. Finally, protein localization studies in MDA-MB-231 cells and HER2-overexpressing mice tumors confirmed that PTPN13 stabilizes intercellular adhesion and promotes desmosome formation. These data provide the first evidence for the negative role of PTPN13 in breast tumor invasiveness and highlight its involvement in cell junction stabilization.

Fig3. Expression of wt (N13-1, N13-2, N13-3) or catalytically inactive (CS) PTPN13 in the indicated cell clones was monitored by western blotting using anti-PTPN13 antibodies.

Fig4. Directional migration was assessed with the wound healing assay. Upper panel: Phase-contrast optical photomicrographs of the wounded area at 0 and 9h. Lower panel: Quantification of cell migration.

PTPN13 has several biochemical functions, for example, phosphatidylinositol 3-kinase regulatory subunit binding,protein binding,protein tyrosine phosphatase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by PTPN13 itself. We selected most functions PTPN13 had, and list some proteins which have the same functions with PTPN13. You can find most of the proteins on our site.

PTPN13 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PTPN13 here. Most of them are supplied by our site. Hope this information will be useful for your research of PTPN13.

RAPGEF6;PKN2;FAS;PLEKHA1;PDCD10