Abstract
Intact osteoactivin, a novel type I membrane glycoprotein, were shed at a dibasic motif in the juxtamembrane region in C2C12 myoblasts. Extracellular fragments were secreted into the culture media by a putative metalloprotease. Extracellular fragments of osteoactivin, but not control protein, induced matrix metalloprotease-3 (MMP-3) expression in NIH-3T3 fibroblasts. Epidermal growth factor (ERK) kinase inhibitors inhibited the osteoactivin-mediated MMP-3 expression, whereas the extracellular fragment of osteoactivin activated ERK1/2 and p38 in the mitogen-activated protein kinase pathway. Our results suggest that the extracellular fragments of osteoactivin produced by shedding act as a growth factor to induce MMP-3 expression via the ERK pathway in fibroblasts.
MeSH terms
-
Animals
-
Enzyme Induction / drug effects
-
Eye Proteins / chemistry
-
Eye Proteins / metabolism*
-
Eye Proteins / pharmacology
-
Fibroblasts / cytology
-
Fibroblasts / drug effects
-
Fibroblasts / enzymology*
-
Male
-
Matrix Metalloproteinase 3 / biosynthesis*
-
Matrix Metalloproteinase 3 / genetics
-
Membrane Glycoproteins / chemistry
-
Membrane Glycoproteins / metabolism*
-
Membrane Glycoproteins / pharmacology
-
Mice
-
Mice, Inbred C57BL
-
Mitogen-Activated Protein Kinase 1 / metabolism*
-
Mitogen-Activated Protein Kinase 3 / metabolism*
-
Muscle, Skeletal / drug effects
-
Muscle, Skeletal / enzymology
-
NIH 3T3 Cells
-
Peptide Fragments / chemistry
-
Peptide Fragments / metabolism*
-
Peptide Fragments / pharmacology
-
Protease Inhibitors / pharmacology
-
Protein Structure, Tertiary
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Up-Regulation / drug effects
Substances
-
Eye Proteins
-
Gpnmb protein, mouse
-
Membrane Glycoproteins
-
Peptide Fragments
-
Protease Inhibitors
-
RNA, Messenger
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Matrix Metalloproteinase 3