Disease relevance of PTPRH

• Gene for the human transmembrane-type protein tyrosine phosphatase H (PTPRH): genomic structure, fine-mapping and its exclusion as a candidate for Peutz-Jeghers syndrome [1].
• In contrast, among cancer cell lines tested, SAP-1 was highly expressed in pancreatic and colorectal cancer cells [2].
• Both immunohistochemical and immunoblot analyses revealed that normal liver tissue, as well as tissue affected by chronic hepatitis or cirrhosis, contained substantial amounts of SAP-1 [3].
• In conclusion, these results indicate that SAP-1 expression is downregulated during the dedifferentiation of human HCC, and that this downregulation may play a causal role in disease progression [3].
• Sap-1/PTPRH, a receptor protein tyrosine phosphatase (RPTP), is a ubiquitously expressed enzyme that is upregulated in human gastrointestinal cancers [4].

High impact information on PTPRH

• The cytoplasmic region of SAP-1 has now been shown to bind directly the tyrosine kinase Lck [5].
• Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function [5].
• Stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1), a transmembrane-type protein-tyrosine phosphatase, is thought to inhibit integrin signaling by mediating the dephosphorylation of focal adhesion-associated proteins [6].
• Adenovirus-mediated overexpression of wild-type SAP-1, but not that of a catalytically inactive mutant of this enzyme, has now been shown to induce apoptosis in NIH 3T3 fibroblasts [6].
• Inhibition of cell growth and spreading by stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1) through dephosphorylation of p130cas [7].

Biological context of PTPRH

• We determined its genomic structure, and performed mutation analysis of all exons and the exon-intron junctions of the PTPRH gene in the PJS07 family [1].
• The full length (3.9 kilobases) of the SAP-1 cDNA was further isolated from the KATO-III cell cDNA library and the WiDr cell cDNA library [2].
• SAP-1 is mapped to chromosome 19 region q13.4 and might be related to carcinoembryonic antigen mapped to 19q13.2 [2].
• In addition, transient transfection of SAP-1 cDNA to COS cells resulted in the predominant expression of a 200-kDa protein recognized by anti-SAP-1 antibody [2].
• Downregulation of stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1) in advanced human hepatocellular carcinoma [3].

Anatomical context of PTPRH

• SAP-1 was mainly expressed in brain and liver and at a lower level in heart and stomach as a 4.2-kilobase mRNA, but it was not detected in pancreas or colon [2].
• These results thus suggest that the direct interaction of SAP-1 with Lck results in inhibition of the kinase activity of the latter and a consequent negative regulation of T cell function [5].
• Expression of recombinant SAP-1 induced the dephosphorylation of p130(cas) as well as that of two other components of the integrin-signaling pathway (focal adhesion kinase and p62(dok)) in intact cells [7].
• Overexpression of SAP-1 induced disruption of the actin-based cytoskeleton as well as inhibited various cellular responses promoted by integrin-mediated cell adhesion, including cell spreading on fibronectin, growth factor-induced activation of extracellular signal-regulated kinase 2, and colony formation [7].

Associations of PTPRH with chemical compounds

• The bacterially expressed SAP-1 fusion protein had tyrosine-specific phosphatase activity [2].

Other interactions of PTPRH

• The extracellular region of SAP-1 consisted of eight fibronectin type III-like structure repeats and contained multiple N-glycosylation sites [2].

Analytical, diagnostic and therapeutic context of PTPRH

• Immunoblotting with anti-SAP-1 antibody showed that SAP-1 is a 200-kDa protein [2].

References