OSTEOGENIC PROTEIN-1 (OP-1) EXPRESSION AND PROCESSING IN CHINESE-HAMSTER OVARY CELLS - ISOLATION OF A SOLUBLE COMPLEX CONTAINING THE MATUREAND PRO-DOMAINS OF OP-1

We have characterized the expression and processing of Osteogenic Prot ein-1 (hOP-1), a bone morphogenic protein of the TGF-beta family, in C hinese hamster ovary cells. The hOP-1 is initially synthesized as a mo nomeric 50 kDa pro-protein that is dimerized, glycosylated, and then p roteolytically cleaved at the Arg-Xaa-Xaa-Arg maturation site in an ac idic cellular compartment before secretion into the medium. Of the fou r potential N-linked glycosylation sites two are used, one in the matu re domain and one in the pro-domain. Gel permeation chromatography of secreted hOP-1 in physiological buffers yields an apparent molecular w eight of 110-120 k, indicating that after proteolytic processing the t wo pro-domains remain non-covalently associated with the disulfide lin ked mature dimer in a complex termed soluble hOP-1 Purified soluble hO P-1 is significantly more soluble in physiological buffers than the pu rified mature OP-1.