Lysyl oxidase binds transforming growth factor-beta and regulates its signaling via amine oxidase activity.
Lysyl oxidase (LOX), an amine oxidase critical for the initiation of collagen and elastin cross-linking, has recently been shown to regulate cellular activities possibly by modulating the functions of growth factors. In this study, we investigated the interaction between LOX and transforming growth factor-beta1 (TGF-beta1), a potent growth factor abundant in bone, the effect of LOX on TGF-beta1 signaling, and its potential mechanism. The specific binding between mature LOX and mature TGF-beta1 was demonstrated by immunoprecipitation and glutathione S-transferase pulldown assay in vitro. Both proteins were colocalized in the extracellular matrix in an osteoblastic cell culture system, and the binding complex was identified in the mineral-associated fraction of bone matrix. Furthermore, LOX suppressed TGF-beta1-induced Smad3 phosphorylation likely through its amine oxidase activity. The data indicate that LOX binds to mature TGF-beta1 and enzymatically regulates its signaling in bone and thus may play an important role in bone maintenance and remodeling.
Atsawasuwan
Phimon
P
Dental Research Center, University of North Carolina at Chapel Hill, North Carolina 27599-7455, USA
Mochida
Yoshiyuki
Y
Katafuchi
Michitsuna
M
Kaku
Masaru
M
Fong
Keith S K
KS
Csiszar
Katalin
K
Yamauchi
Mitsuo
M
D016475:3T3 Cells; D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D010006:Osteoblasts / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D008249:Protein-Lysine 6-Oxidase; D006631:Amine Oxidase (Copper-Containing); D005982:Glutathione Transferase