Cloning and Characterization of Islet Cell Antigen-related Protein-tyrosine Phosphatase (PTP), a Novel Receptor-like PTP and Autoantigen in Insulin-dependent Diabetes

Henry J. DeAizpurua,Lin Cui,Robert S. Schmidli,Wei-Ping Yu,Catherine J. Pallen

doi:10.1074/jbc.271.40.24817

Abstract

Cloning of the cDNA encoding a novel human protein- tyrosine phosphatase (PTP) called islet cell antigen-related PTP (IAR) predicts a receptor-like molecule with an extracellular domain of 614 amino acids containing a hydrophobic signal peptide, one potential N-glycosylation site, and an RGDS peptide which is a possible adhesive recognition sequence. The 376-amino acid intracellular region contains a single catalytic domain. Recombinant IAR polypeptide has phosphatase activity. Northern blot analysis shows tissue-specific expression of two IAR transcripts of 5.5 and 3. 7 kilobases, which are most abundant in brain and pancreas. The IAR PTP is homologous in its intracellular region to IA-2, a putative PTP that is an insulin-dependent diabetes mellitus (IDDM) autoantigen. IAR is also reactive with IDDM patient sera. IAR and IA-2 may distinguish different populations of IDDM autoantibodies since they identify overlapping but nonidentical sets of IDDM patients. Thus IAR is likely to be an islet cell antigen useful in the preclinical screening of individuals for risk of IDDM.

Highlights

Cloning of the cDNA encoding a novel human proteintyrosine phosphatase (PTP) called islet cell antigen-related protein tyrosine kinases and phosphatases (PTPs) (IAR) predicts a receptor-like molecule with an extracellular domain of 614 amino acids containing a hydrophobic signal peptide, one potential N-glycosylation site, and an RGDS peptide which is a possible adhesive recognition sequence
The receptorlike PTPs consist of an intracellular region with the catalytic domains, a transmembrane region, and an extracellular region that often, but not always, contains structural motifs found in cell adhesion such as FN-III and Ig-like repeats
islet cell antigen-related PTP (IAR) is a member of a related group of receptor-like PTPs that includes IA-2 and PTPLP [16, 22, 24]

Summary

Introduction

Cloning of the cDNA encoding a novel human proteintyrosine phosphatase (PTP) called islet cell antigen-related PTP (IAR) predicts a receptor-like molecule with an extracellular domain of 614 amino acids containing a hydrophobic signal peptide, one potential N-glycosylation site, and an RGDS peptide which is a possible adhesive recognition sequence. We report here the cloning and characterization of a human receptor-like PTP, termed IAR, which is reactive with IDDM sera.

Results

Conclusion