MAP kinase phosphatase-1 is induced in abnormal fibers in inclusion body myositis.
Mots clés
Abstrait
OBJECTIVE
To investigate alterations in protein kinases and phosphatases that regulate the activity of mitogen activated protein kinase (MAPK) in sporadic inclusion body myositis (IBM).
BACKGROUND
In vacuolated fibers in IBM, several studies reported upregulation of the extracellular regulated kinase (ERK) subclass of MAPK family. Whereas MAPK kinases (MKK) activate MAPK, MAPK phosphatases (MKP) inactivate MAPK. MKP-1 is involved in muscle fiber differentiation and it is downregulated during myotube formation.
METHODS
Immunolocalization of MKK1 through MKK4 and MKP-1 to MKP-3 was tested in muscle specimens from 10 patients with IBM and controls.
RESULTS
In IBM, strong and focal deposits of MKP-1 were observed in vacuolated fibers. The MKP-1-positive deposits were colocalized with ERK. MKP-2, MKP-3, and MKK were not associated with vacuolated fibers.
CONCLUSIONS
In IBM, MKP-1 is abnormally induced in vacuolated fibers probably to inactivate ERK. Although direct activators other than those tested in the current study might induce ERK, the absence of activation of MKK suggests that the aggregation of ERK protein itself causes the seeming upregulation of the protein kinase in IBM. Like ERK and its nuclear substrate, MKP-1 is an enzyme that forms aggregates in vacuolated fibers and is involved in myogenesis.
