LATENT TRANSFORMING GROWTH-FACTOR-BETA COMPLEX IN CHINESE-HAMSTER OVARY CELLS CONTAINS THE MULTIFUNCTIONAL CYSTEINE-RICH FIBROBLAST GROWTH-FACTOR RECEPTOR, ALSO TERMED E-SELECTIN-LIGAND OR MG-160

Transforming growth factor-beta (TGF-beta) is secreted as latent high molecular mass complexes from producer cells. The N-terminal precursor remnant, also called latency-associated peptide (LAP), forms a non-co valently linked complex with TGF-beta and confers the latency to TGF-b eta. In human platelets and certain other cell types, latent TGF-beta binding protein-1 (LTBP-1) is disulphide-linked to LAP, and forms comp lexes of more than 230 kDa. In addition, LTBP-2 and -3, which are stru cturally similar to LTBP-1, can be part of latent TGF-beta complexes. In Chinese hamster ovary (CHO) cells transfected with the TGF-beta 1 c DNA, a major part of the latent TGF-beta secreted into the medium is a 100-kDa small latent complex containing TGF-beta and LAP. In addition , we found two other forms of latent TGF-beta complexes, i.e. a 220-kD a complex containing LTBP-1, and a 220-kDa complex containing a 140-kD a protein. Purification of the 140-kDa component, termed latent TGF-be ta complexed protein-1. (LTCP-1), followed by amino acid sequencing an d cDNA cloning from a CHO cell cDNA library, revealed that it is a ham ster counterpart of a previously identified, multifunctional protein k nown as chicken cysteine-rich fibroblast growth factor (FGF) receptor, mouse E-selectin-ligand and rat MG-160 (a 160-kDa membrane sialoglyco protein of the Golgi apparatus). Immunoprecipitation of LTCP-1 and TGF -beta from CHO cells stably transfected with TGF-beta 1 precursor cDNA revealed that the expressed protein forms a complex with LAP, and tha t a major part of the complex is secreted. Northern blot analysis show ed that mRNA for LTCP-1 was expressed in large amounts in testis, ovar y and placenta, but less abundantly in other tissues. These results su ggest that TGF-beta, produced in certain cell types, may form a comple x with LTCP-1, which may have different properties compared with other latent TGF-beta complexes. It remains to be investigated whether the complex formation between LTCP-1 and TGF-beta 1 also occurs in other c ells, whether the association between them occurs in the Golgi complex , and whether it affects the interaction of LTCP-1 with FGF or E-selec tin.