Role of lysyl oxidase propeptide in secretion and enzyme activity.
Lysyl oxidase (LOX) is secreted as a proenzyme (proLOX) that is proteolytically processed in the extracellular milieu to release the propeptide and mature, active LOX. LOX oxidizes lysyl residues of a number of protein substrates in the extracellular matrix and on the cell surface, which impacts several physiological and disease states. Although the LOX propeptide (LOX-PP) is glycosylated, little is known about the role of this modification in LOX secretion and activity. To gain insight into this issue, cells were transfected with native, full-length LOX cDNA (pre-pro-LOX), the N-glycosylation null pre-[N/Q]pro-LOX cDNA and the deletion mutant pre-LOX cDNA, referred to as secretory LOX, in which mature LOX is targeted to the secretory pathway without its N-terminal propeptide sequence. The results show that glycosylation of the LOX-PP is not required for secretion and extracellular processing of pro-LOX but it is required for optimal enzyme activity of the resulting mature LOX. Complete deletion of the propeptide sequence prevents mature LOX from exiting the endoplasmic reticulum (ER). Taken together, our study points out the requirement of the LOX-PP for pro-LOX exit from the ER and is the first to highlight the influence of LOX-PP glycosylation on LOX enzyme activity.
Grimsby
Jessica L
JL
Division of Oral Biology, Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Lucero
Hector A
HA
Trackman
Philip C
PC
Ravid
Katya
K
Kagan
Herbert M
HM
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D021381:Protein Transport; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection
D018076:DNA, Complementary; D004792:Enzyme Precursors; D008249:Protein-Lysine 6-Oxidase