Denervation enhances the expression of SHPS-1 in rat skeletal muscle.
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.
Mitsuhashi
Hiroaki
H
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902.
Yoshikawa
Ayumu
A
Sasagawa
Noboru
N
Hayashi
Yukiko
Y
Ishiura
Shoichi
S
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000378:metabolism*; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015854:Up-Regulation; D018909:src Homology Domains
D000943:Antigens, Differentiation; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C501924:Sirpa protein, rat; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases