Transforming growth factor-β (TGF-β) 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-covalently linked complex with TGF-β and confers the latency to TGF-β. In human platelets and certain other cell types, latent TGF-β binding protein-1 (LTBP-1) is disulphide-linked to LAP, and forms complexes of more than 230 kDa. In addition, LTBP-2 and -3, which are structurally similar to LTBP-1, can be part of latent TGF-β complexes. In Chinese hamster ovary (CHO) cells transfected with the TGF-β1 cDNA, a major part of the latent TGF-β secreted into the medium is a 100-kDa small latent complex containing TGF-β and LAP. In addition, we found two other forms of latent TGF-β complexes, i.e. a 220-kDa complex containing LTBP-1, and a 220-kDa complex containing a 140-kDa protein. Purification of the 140-kDa component, termed latent TGF-β complexed protein-1 (LTCP-1), followed by amino acid sequencing and cDNA cloning from a CHO cell cDNA library, revealed that it is a hamster counterpart of a previously identified, multifunctional protein known as chicken cysteine-rich fibroblast growth factor (FGF) receptor, mouse E-selectin-ligand and rat MG-160 (a 160-kDa membrane sialoglycoprotein of the Golgi apparatus). Immunoprecipitation of LTCP-1 and TGF-β1 from CHO cells stably transfected with TGF-β1 precursor cDNA revealed that the expressed protein forms a complex with LAP, and that a major part of the complex is secreted. Northern blot analysis showed that mRNA for LTCP-1 was expressed in large amounts in testis, ovary and placenta, but less abundantly in other tissues. These results suggest that TGF-β, produced in certain cell types, may form a complex with LTCP-1, which may have different properties compared with other latent TGF-β complexes. It remains to be investigated whether the complex formation between LTCP-1 and TGF-β1 also occurs in other cells, whether the association between them occurs in the Golgi complex, and whether it affects the interaction of LTCP-1 with FGF or E-selectin.
Latent transforming growth factor-β complex in Chinese hamster ovary cells contains the multifunctional cysteine-rich fibroblast growth factor receptor, also termed E-selectin-ligand or MG-160
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Anders OLOFSSON, Ulf HELLMAN, Peter TEN DIJKE, Susanne GRIMSBY, Hidenori ICHIJO, Anita MORÉN, Kohei MIYAZONO, Carl-Henrik HELDIN; Latent transforming growth factor-β complex in Chinese hamster ovary cells contains the multifunctional cysteine-rich fibroblast growth factor receptor, also termed E-selectin-ligand or MG-160. Biochem J 1 June 1997; 324 (2): 427–434. doi: https://doi.org/10.1042/bj3240427
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