© 2005 The Japanese Biochemical Society
Regular Paper |
Denervation Enhances the Expression of SHPS-1 in Rat Skeletal Muscle
1 Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902; and 2 Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502
* To whom correspondence should be addressed. Tel/Fax: +81-3-5454-6739, E-mail: cishiura{at}mail.ecc.u-tokyo.ac.jp
SHPS-1 (Src homology 2 domain containing protein tyrosine phosphatase substrate 1) is a transmembrane glycoprotein containing three immunoglobulin-like motifs in its extracellular domain and immunoreceptor tyrosine–based inhibitory motifs (ITIM) that interact with SHP-2 (Src homology 2 domain containing protein tyrosine phosphatase-2) in its cytoplasmic region. SHPS-1 is highly expressed in brain, but at much lower levels in skeletal muscle. In this study, we found that the level of the SHPS-1 mRNA increases in rat skeletal muscle after denervation. Western blot analysis also confirmed the increase of SHPS-1 in denervated muscle. Moreover, it was found that the glycosylation of SHPS-1 is N-linked in a muscle-specific manner, and that this is altered upon innervation or denervation. Immunohistochemistry revealed SHPS-1 immunoreactivity at neuromuscular junctions (NMJs) under innervation, whereas immunoreactivity was observed extrasynaptically in muscle fibers after denervation. Our results indicate that the expression, glycosylation, and localization of SHPS-1 are strongly regulated by the nervous system, and that SHPS-1 may play an important role in denervated skeletal muscle.