Proliferating and migrating mesangial cells responding to injury express a novel receptor protein-tyrosine phosphatase in experimental mesangial proliferative glomerulonephritis.
The mesangial cell provides structural support to the kidney glomerulus. A polymerase chain reaction-based cDNA display approach identified a novel protein-tyrosine phosphatase, rPTP-GMC1, whose transcript expression is transiently and dramatically up-regulated during the period of mesangial cell migration and proliferation that follows mesangial cell injury in the anti-Thy 1 model of mesangial proliferative glomerulonephritis in the rat. In situ hybridization analysis confirmed that rPTP-GMC1 mRNA is up-regulated specifically by mesangial cells responding to the injury and is not detectable in other cells in the kidney or in many normal tissues. In cell culture, rPTP-GMC1 is expressed by mesangial cells but not by glomerular endothelial or epithelial cells (podocytes). The longest transcript (7.5 kilobases) encodes a receptor-like protein-tyrosine phosphatase consisting of a single catalytic domain, a transmembrane segment, and 18 fibronectin type III-like repeats in the extracellular segment. A splice variant predicts a truncated molecule missing the catalytic domain. rPTP-GMC1 maps to human chromosome 12q15 and to the distal end of mouse chromosome 10. The predicted structure of rPTP-GMC1 and its pattern of expression in vivo and in culture suggest that it plays a role in regulating the adhesion and migration of mesangial cells in response to injury.
Wright
M B
MB
Department of Pathology, University of Washington, Seattle, Washington 98105-7470, USA.
Hugo
C
C
Seifert
R
R
Disteche
C M
CM
Bowen-Pope
D F
DF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D016384:Consensus Sequence; D018076:DNA, Complementary; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D015432:Glomerulonephritis, Membranoproliferative / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000293:injuries / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009115:Muridae; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D018076:DNA, Complementary; D012333:RNA, Messenger; D017027:Protein Tyrosine Phosphatases; C114681:Ptprq protein, rat; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3