Disease relevance of Ptprn2

• An insulin granule membrane protein-tyrosine phosphatase (PTP) homologue, phogrin, was cloned by expression screening of a rat insulinoma cDNA library [1].
• Antibodies to phogrin were detected in sera from patients with IDDM, and these antibodies were strongly correlated with the presence of antibodies to the 37-kDa antigen [2].

High impact information on Ptprn2

• Phogrin was labeled with GFP at its luminal end and used to sense the pH in granules [3].
• IA-2 and phogrin are tyrosine phosphatase-like proteins that may mediate interactions between secretory granules and cytoskeleton in islets and neuroendocrine tissues [4].
• Islet content of IA-2, but not phogrin, increased during the first 10 days of life in rats, when insulin secretion in response to glucose increased to adult levels [4].
• Different regulated expression of the tyrosine phosphatase-like proteins IA-2 and phogrin by glucose and insulin in pancreatic islets: relationship to development of insulin secretory responses in early life [4].
• Molecular cloning of phogrin, a protein-tyrosine phosphatase homologue localized to insulin secretory granule membranes [1].

Chemical compound and disease context of Ptprn2

• Identification of the 37-kDa antigen in IDDM as a tyrosine phosphatase-like protein (phogrin) related to IA-2 [2].
• To image the behaviour in real time of single secretory granules in neuroendocrine cells we have expressed cDNA encoding a fusion construct between the dense-core secretory-granule-membrane glycoprotein, phogrin (phosphatase on the granule of insulinoma cells), and enhanced green fluorescent protein (EGFP) [5].

Biological context of Ptprn2

• PTP NE-6: a brain-enriched receptor-type protein tyrosine phosphatase with a divergent catalytic domain [6].
• The predicted amino acid sequence demonstrates that PTP NE-6 contains a single catalytic domain that diverges from the consensus protein tyrosine phosphatase catalytic domain by expressing an aspartate instead of the conserved alanine residue in the catalytic site [6].
• These results demonstrate that the 37-kDa antigen in IDDM is indistinguishable from phogrin and show that two distinct tyrosine phosphatase-related proteins are major targets of the autoimmune response in the disease [2].

Anatomical context of Ptprn2

• In situ hybridization demonstrates that PTP NE-6 mRNA is expressed throughout the brain, with highest levels in the medial habenula and at intermediate levels in layer IV of cortex, medial geniculate nucleus, inferior colliculus, hypothalamus, and thalamus [6].
• PTP NE-6 mRNA is abundant in brain and expressed at lower levels in olfactory tissue and adrenal gland [6].

Associations of Ptprn2 with chemical compounds

• These data demonstrate that the inactivity of native PTP NE-6 toward p-nitrophenyl phosphate is due to the divergent aspartate in the catalytic site and not to variant amino acids within the phosphatase domain [6].

Other interactions of Ptprn2

• A receptor-type protein tyrosine phosphatase, PTP NE-6, was identified from rat olfactory epithelial cDNA and cloned from a rat brain cDNA library [6].
• In situ experiments in rat brain showing the distribution of IA-2 and phogrin suggested a complimentary and overlapping pattern compared with the proprotein convertases PC1 and PC2 [7].

Analytical, diagnostic and therapeutic context of Ptprn2

• We have developed a radioimmunoassay for detecting antiphogrin autoantibodies using in vitro transcribed and translated phogrin and have established the sensitivity and specificity of this assay [8].

References