Molecular cloning of phogrin, a protein-tyrosine phosphatase homologue localized to insulin secretory granule membranes.

Abstract

An insulin granule membrane protein-tyrosine phosphatase (PTP) homologue, phogrin, was cloned by expression screening of a rat insulinoma cDNA library. The 3723-base pair cDNA encoded a transmembrane glycoprotein of 1004 amino acids (Mr 111876) that underwent post-translational proteolysis to 60-64-kDa products after a 30-min delay. The kinetics of proteolytic conversion (t1/2 = 45 min) and turnover (t1/2 = 12 h) were consistent with sorting and conversion in a late compartment of the secretory pathway. Studies on the native beta-cell protein suggested that the COOH-terminal PTP domain was on the cytosolic face of the secretory granule. The lumenal segment was comprised of a protease-resistant globular domain of around 25 kDa. Its localization and topology is thus consistent with a transmembrane receptor function related to granule biogenesis, exocytosis, or subsequent membrane recovery, and it should prove to be a useful cell biological marker for the granule membrane. High expression of the mRNA (5.4 kilobases) and protein was evident in islets, pancreatic alpha- and beta-cell tumor lines, brain cells, and other cells of neuroendocrine lineage. It is closely related to the diabetic autoantigen ICA512 (IA-2) (42% identity overall; 80% in the 260-amino acid PTP domain) and thus a potential target of autoimmunity in diabetes mellitus.

• Authors: C Wasmeier, J C Hutton
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 271 Issue 30 Pg. 18161-70 (Jul 26 1996) ISSN: 0021-9258 [Print] United States
• PMID: 8663434 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• DNA, Complementary
• Membrane Glycoproteins
• Membrane Proteins
• Neoplasm Proteins
• RNA, Messenger
• PTPRN protein, human
• PTPRN2 protein, human
• Protein Tyrosine Phosphatases
• Ptprn protein, rat
• Receptor-Like Protein Tyrosine Phosphatases, Class 8

Topics

• Amino Acid Sequence
• Animals
• Autoantigens
• Base Sequence
• Cell Compartmentation
• Cloning, Molecular
• Cytoplasmic Granules (enzymology)
• DNA, Complementary (genetics)
• Insulinoma
• Intracellular Membranes (enzymology)
• Islets of Langerhans (enzymology)
• Membrane Glycoproteins (genetics)
• Membrane Proteins (genetics)
• Molecular Sequence Data
• Neoplasm Proteins (genetics)
• Protein Tyrosine Phosphatases (genetics)
• RNA, Messenger (analysis)
• Rats
• Receptor-Like Protein Tyrosine Phosphatases, Class 8
• Sequence Analysis, DNA
• Sequence Homology, Amino Acid
• Tissue Distribution
• Tumor Cells, Cultured