A role for SHPS-1/SIRPalpha in Concanavalin A-dependent production of MMP-9.
SHPS-1/SIRPalpha1 is a transmembrane glycoprotein that belongs to the immunoglobulin (Ig) super family. In the present study, we show that SHPS-1 strongly associates with Concanavalin A (Con A), a plant lectin obtained from jack beans. Further studies with SHPS-1 mutants reveal that the extracellular domain of SHPS-1 containing the Ig sequence is responsible for its association with Con A. Con A treatment induces cross-linking and multimerization of the SHPS-1 protein in the plasma membrane, accompanied by its tyrosine phosphorylation and recruitment of SHP-2. In contrast, Ricinus communis agglutinin (RCA), another lectin obtained from castor bean, does not bind or activate tyrosine phosphorylation of SHPS-1. Moreover, Con A activates Akt in a SHP-2-dependent manner. Treatment of mouse embryonic fibroblasts (MEFs) with Con A induces secretion of matrix metalloproteinase (MMP)-9, a phenomenon that is inhibited in cells expressing YF mutant of SHPS-1, a dominant negative form of Akt or in cells pre-treated with an Akt inhibitor, LY294002 or extracellular-signal regulated kinase (Erk) inhibitor, U0126. In addition, expression of the YF mutant of SHPS-1 inhibits Con A-dependent activation of Akt and Erk kinases. Taken together, our results suggest that SHPS-1 is a receptor for Con A that mediates Con A-dependent MMP-9 secretion through SHP-2-promoted activation of both Akt and Erk pathways.
Ruhul Amin
A R M
AR
Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Uddin Biswas
M Helal
MH
Senga
Takeshi
T
Feng
Gen-Sheng
GS
Kannagi
Reiji
R
Agarwal
Munna L
ML
Hamaguchi
Michinari
M
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003208:Concanavalin A / Q000378:metabolism / Q000494:pharmacology*; D004628:Embryonic Structures / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D010766:Phosphorylation; D037121:Plant Lectins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism