Isoform-specific transforming growth factor-beta binding proteins with membrane attachments sensitive to phosphatidylinositol-specific phospholipase C

• Published in: The Journal of biological chemistry 1991-11, Vol.266 (31), p.20767-20772
• Main Authors: Cheifetz, S., Massagué, J.
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Binding and carrier proteins; Binding, Competitive; Biological and medical sciences; Cattle; Cell Line; Disulfides; Dithiothreitol - pharmacology; Fundamental and applied biological sciences. Psychology; Membrane Glycoproteins - metabolism; Molecular Weight; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoinositide Phospholipase C; phospholipase C; Phosphoric Diester Hydrolases - metabolism; Proteins; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta - classification; Transforming Growth Factor beta - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)54774-8

We report the identification of cell surface glycoproteins that bind transforming growth factor-beta (TGF-beta) in an isoform-specific manner, and are distinct from TGF-beta receptors I and II or the TGF-beta binding proteoglycan beta-glycan. The novel TGF-beta binding proteins have been identified in various cell lines including fetal bovine heart endothelial cells and MG-63 human osteosarcoma cells. They include proteins of 90-100 and 180 kDa that preferentially bind TGF-beta 1 (KD 0.1-0.2 nM) and proteins of 60 and 140 kDa that preferentially bind TGF-beta 2 (KD 0.5-1 nM). The 180-kDa TGF-beta 1 binding protein and the 60- and 140-kDa TGF-beta 2 binding proteins can be released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C, suggesting that these proteins are attached to the plasma membrane through a phosphatidylinositol anchor. The expression of these three proteins as well as their sensitivity to phosphatidylinositol-specific phospholipase C is cell line-dependent. The 90-100-kDa TGF-beta 1 binding proteins are components of a 190-kDa disulfide-linked complex. The structural properties of these proteins and their high affinity and selectivity for different TGF-beta isoforms defines them as a novel class of cell surface TGF-beta binding proteins.