title: Association of active extracellular signal-regulated protein kinase with paired helical filaments of inclusion-body myositis muscle suggests its role in inclusion-body myositis tau phosphorylation.
abstract: The possible role of extracellular signal-regulated kinase (ERK) in the pathogenesis of inclusion-body myositis (IBM) was investigated by immunostaining the active phosphorylated form of ERK in muscle biopsies of six IBM and 14 control patients. Between 80% and 90% of IBM vacuolated muscle fibers contained well-defined ERK-immunoreactive inclusions, which were co-localized by light microscopy, with phosphorylated tau in 70 to 80% of those fibers. Immunoelectronmicroscopy colocalized ERK to small amorphous tufts adjacent to the muscle fiber paired-helical filaments. Strong ERK immunoreactivity was also present at the postsynaptic domain of all human neuromuscular junctions. Our study suggests 1) that ERK, a signal transducer, might play a role in IBM pathogenesis, including participation in the pathological phosphorylation of IBM tau; and 2) that signal transduction abnormalities may be a component of the IBM pathogenic cascade. Our novel immunolocalization of ERK at the postsynaptic domain of human neuromuscular junctions supports a role in transcription of junctional-protein genes. The ERK localized in nonjunctional regions of IBM fibers may underlie the known pathological up-regulation of junctional proteins there.
authors.affiliation: Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA 90017-1912, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Wilczynski
authors.forename: W K
authors.initials: WK
authors.lastname: Engel
authors.forename: V
authors.initials: V
authors.lastname: Askanas
mesh_terms: D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D018979:Myositis, Inclusion Body / Q000378:metabolism* / Q000473:pathology; D019600:Neuropil Threads / Q000378:metabolism*; D010766:Phosphorylation; D012016:Reference Values; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D020928:Mitogen-Activated Protein Kinases