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.
Dental Research Center, University of North Carolina at Chapel Hill, North Carolina 27599-7455, USA
Phimon
P
Atsawasuwan
Yoshiyuki
Y
Mochida
Michitsuna
M
Katafuchi
Masaru
M
Kaku
Keith S K
KS
Fong
Katalin
K
Csiszar
Mitsuo
M
Yamauchi
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